Mice homozygous for the mutant autosomal recessive gene "scid" which is located on the centromeric end of chromosome 16. These mice lack mature, functional lymphocytes and are thus highly susceptible to lethal opportunistic infections if not chronically treated with antibiotics. The lack of B- and T-cell immunity resembles severe combined immunodeficiency (SCID) syndrome in human infants. SCID mice are useful as animal models since they are receptive to implantation of a human immune system producing SCID-human (SCID-hu) hematochimeric mice.
A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.
A mutation in which a codon is mutated to one directing the incorporation of a different amino acid. This substitution may result in an inactive or unstable product. (From A Dictionary of Genetics, King & Stansfield, 5th ed)
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
A type of mutation in which a number of NUCLEOTIDES deleted from or inserted into a protein coding sequence is not divisible by three, thereby causing an alteration in the READING FRAMES of the entire coding sequence downstream of the mutation. These mutations may be induced by certain types of MUTAGENS or may occur spontaneously.
Any detectable and heritable alteration in the lineage of germ cells. Mutations in these cells (i.e., "generative" cells ancestral to the gametes) are transmitted to progeny while those in somatic cells are not.
The record of descent or ancestry, particularly of a particular condition or trait, indicating individual family members, their relationships, and their status with respect to the trait or condition.
The number of mutations that occur in a specific sequence, GENE, or GENOME over a specified period of time such as years, CELL DIVISIONS, or generations.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. It is inherited as an X-linked or autosomal recessive defect. Mutations occurring in many different genes cause human Severe Combined Immunodeficiency (SCID).
The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.
An individual having different alleles at one or more loci regarding a specific character.
The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Biochemical identification of mutational changes in a nucleotide sequence.
Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.
Variation in a population's DNA sequence that is detected by determining alterations in the conformation of denatured DNA fragments. Denatured DNA fragments are allowed to renature under conditions that prevent the formation of double-stranded DNA and allow secondary structure to form in single stranded fragments. These fragments are then run through polyacrylamide gels to detect variations in the secondary structure that is manifested as an alteration in migration through the gels.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.
An individual in which both alleles at a given locus are identical.
An amino acid-specifying codon that has been converted to a stop codon (CODON, TERMINATOR) by mutation. Its occurance is abnormal causing premature termination of protein translation and results in production of truncated and non-functional proteins. A nonsense mutation is one that converts an amino acid-specific codon to a stop codon.
Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.
A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.
Genes that influence the PHENOTYPE only in the homozygous state.
Deletion of sequences of nucleic acids from the genetic material of an individual.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
Genes that influence the PHENOTYPE both in the homozygous and the heterozygous state.
Detection of a MUTATION; GENOTYPE; KARYOTYPE; or specific ALLELES associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
Established cell cultures that have the potential to propagate indefinitely.
A strain of non-obese diabetic mice developed in Japan that has been widely studied as a model for T-cell-dependent autoimmune insulin-dependent diabetes mellitus in which insulitis is a major histopathologic feature, and in which genetic susceptibility is strongly MHC-linked.
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
Mutation process that restores the wild-type PHENOTYPE in an organism possessing a mutationally altered GENOTYPE. The second "suppressor" mutation may be on a different gene, on the same gene but located at a distance from the site of the primary mutation, or in extrachromosomal genes (EXTRACHROMOSOMAL INHERITANCE).
Any method used for determining the location of and relative distances between genes on a chromosome.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (CODON, TERMINATOR). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, TRANSFER) complementary to all codons. These codons are referred to as unassigned codons (CODONS, NONSENSE).
The parts of a macromolecule that directly participate in its specific combination with another molecule.
Transplantation between animals of different species.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
A test used to determine whether or not complementation (compensation in the form of dominance) will occur in a cell with a given mutant phenotype when another mutant genome, encoding the same mutant phenotype, is introduced into that cell.
A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
Tumor suppressor genes located on the short arm of human chromosome 17 and coding for the phosphoprotein p53.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
A phenomenon that is observed when a small subgroup of a larger POPULATION establishes itself as a separate and isolated entity. The subgroup's GENE POOL carries only a fraction of the genetic diversity of the parental population resulting in an increased frequency of certain diseases in the subgroup, especially those diseases known to be autosomal recessive.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
A characteristic symptom complex.
The co-inheritance of two or more non-allelic GENES due to their being located more or less closely on the same CHROMOSOME.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.
The magnitude of INBREEDING in humans.
Proteins produced from GENES that have acquired MUTATIONS.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.
A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.
A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
Proteins found in any species of bacterium.
Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.
Syndromes in which there is a deficiency or defect in the mechanisms of immunity, either cellular or humoral.
Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses.
Mice bearing mutant genes which are phenotypically expressed in the animals.
Genes whose loss of function or gain of function MUTATION leads to the death of the carrier prior to maturity. They may be essential genes (GENES, ESSENTIAL) required for viability, or genes which cause a block of function of an essential gene at a time when the essential gene function is required for viability.
Mutagenesis where the mutation is caused by the introduction of foreign DNA sequences into a gene or extragenic sequence. This may occur spontaneously in vivo or be experimentally induced in vivo or in vitro. Proviral DNA insertions into or adjacent to a cellular proto-oncogene can interrupt GENETIC TRANSLATION of the coding sequences or interfere with recognition of regulatory elements and cause unregulated expression of the proto-oncogene resulting in tumor formation.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
Identification of genetic carriers for a given trait.
That part of the genome that corresponds to the complete complement of EXONS of an organism or cell.
Double-stranded DNA of MITOCHONDRIA. In eukaryotes, the mitochondrial GENOME is circular and codes for ribosomal RNAs, transfer RNAs, and about 10 proteins.
A raf kinase subclass found at high levels in neuronal tissue. The B-raf Kinases are MAP kinase kinase kinases that have specificity for MAP KINASE KINASE 1 and MAP KINASE KINASE 2.
A tumor suppressor gene (GENES, TUMOR SUPPRESSOR) located on human CHROMOSOME 17 at locus 17q21. Mutations of this gene are associated with the formation of HEREDITARY BREAST AND OVARIAN CANCER SYNDROME. It encodes a large nuclear protein that is a component of DNA repair pathways.
The health status of the family as a unit including the impact of the health of one member of the family on the family as a unit and on individual family members; also, the impact of family organization or disorganization on the health status of its members.
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
DNA present in neoplastic tissue.
Transport proteins that carry specific substances in the blood or across cell membranes.
Proteins prepared by recombinant DNA technology.
Sequences of DNA in the genes that are located between the EXONS. They are transcribed along with the exons but are removed from the primary gene transcript by RNA SPLICING to leave mature RNA. Some introns code for separate genes.
The proportion of one particular in the total of all ALLELES for one genetic locus in a breeding POPULATION.
Genotypic differences observed among individuals in a population.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
The functional hereditary units of BACTERIA.
The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Deliberate breeding of two different individuals that results in offspring that carry part of the genetic material of each parent. The parent organisms must be genetically compatible and may be from different varieties or closely related species.
The rate dynamics in chemical or physical systems.
A variety of simple repeat sequences that are distributed throughout the GENOME. They are characterized by a short repeat unit of 2-8 basepairs that is repeated up to 100 times. They are also known as short tandem repeats (STRs).
The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.
The ability of viruses to resist or to become tolerant to chemotherapeutic agents or antiviral agents. This resistance is acquired through gene mutation.
A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.
An ethnic group with historical ties to the land of ISRAEL and the religion of JUDAISM.
The age, developmental stage, or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual.
Genes that have a suppressor allele or suppressor mutation (SUPPRESSION, GENETIC) which cancels the effect of a previous mutation, enabling the wild-type phenotype to be maintained or partially restored. For example, amber suppressors cancel the effect of an AMBER NONSENSE MUTATION.
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
A nitrosourea compound with alkylating, carcinogenic, and mutagenic properties.
CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)
A cell line derived from cultured tumor cells.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
A sequence of amino acids in a polypeptide or of nucleotides in DNA or RNA that is similar across multiple species. A known set of conserved sequences is represented by a CONSENSUS SEQUENCE. AMINO ACID MOTIFS are often composed of conserved sequences.
Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes.
A mutation named with the blend of insertion and deletion. It refers to a length difference between two ALLELES where it is unknowable if the difference was originally caused by a SEQUENCE INSERTION or by a SEQUENCE DELETION. If the number of nucleotides in the insertion/deletion is not divisible by three, and it occurs in a protein coding region, it is also a FRAMESHIFT MUTATION.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Experimental transplantation of neoplasms in laboratory animals for research purposes.
Genetic diseases that are linked to gene mutations on the X CHROMOSOME in humans (X CHROMOSOME, HUMAN) or the X CHROMOSOME in other species. Included here are animal models of human X-linked diseases.
The reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule which contained damaged regions. The major repair mechanisms are excision repair, in which defective regions in one strand are excised and resynthesized using the complementary base pairing information in the intact strand; photoreactivation repair, in which the lethal and mutagenic effects of ultraviolet light are eliminated; and post-replication repair, in which the primary lesions are not repaired, but the gaps in one daughter duplex are filled in by incorporation of portions of the other (undamaged) daughter duplex. Excision repair and post-replication repair are sometimes referred to as "dark repair" because they do not require light.
Variation occurring within a species in the presence or length of DNA fragment generated by a specific endonuclease at a specific site in the genome. Such variations are generated by mutations that create or abolish recognition sites for these enzymes or change the length of the fragment.
The percent frequency with which a dominant or homozygous recessive gene or gene combination manifests itself in the phenotype of the carriers. (From Glossary of Genetics, 5th ed)
Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.
Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.
The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms.
Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.
Hereditary, progressive degeneration of the neuroepithelium of the retina characterized by night blindness and progressive contraction of the visual field.
A tumor suppressor gene (GENES, TUMOR SUPPRESSOR) located on human chromosome 13 at locus 13q12.3. Mutations in this gene predispose humans to breast and ovarian cancer. It encodes a large, nuclear protein that is an essential component of DNA repair pathways, suppressing the formation of gross chromosomal rearrangements. (from Genes Dev 2000;14(11):1400-6)
The ultimate exclusion of nonsense sequences or intervening sequences (introns) before the final RNA transcript is sent to the cytoplasm.
Nucleotide sequences located at the ends of EXONS and recognized in pre-messenger RNA by SPLICEOSOMES. They are joined during the RNA SPLICING reaction, forming the junctions between exons.
Differential and non-random reproduction of different genotypes, operating to alter the gene frequencies within a population.
The functional hereditary units of FUNGI.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
The process of cumulative change at the level of DNA; RNA; and PROTEINS, over successive generations.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to alpha helices, beta strands (which align to form beta sheets) or other types of coils. This is the first folding level of protein conformation.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.
A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.
A large, nuclear protein, encoded by the BRCA2 gene (GENE, BRCA2). Mutations in this gene predispose humans to breast and ovarian cancer. The BRCA2 protein is an essential component of DNA repair pathways, suppressing the formation of gross chromosomal rearrangements. (from Genes Dev. 2000;14(11):1400-6)
A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey (C. pygerythrus) is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research.
Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.
Proteins found in any species of fungus.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
Small, monomeric GTP-binding proteins encoded by ras genes (GENES, RAS). The protooncogene-derived protein, PROTO-ONCOGENE PROTEIN P21(RAS), plays a role in normal cellular growth, differentiation and development. The oncogene-derived protein (ONCOGENE PROTEIN P21(RAS)) can play a role in aberrant cellular regulation during neoplastic cell transformation (CELL TRANSFORMATION, NEOPLASTIC). This enzyme was formerly listed as EC 3.6.1.47.
Proteins obtained from ESCHERICHIA COLI.
Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.
Discrete segments of DNA which can excise and reintegrate to another site in the genome. Most are inactive, i.e., have not been found to exist outside the integrated state. DNA transposable elements include bacterial IS (insertion sequence) elements, Tn elements, the maize controlling elements Ac and Ds, Drosophila P, gypsy, and pogo elements, the human Tigger elements and the Tc and mariner elements which are found throughout the animal kingdom.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
A species of fruit fly much used in genetics because of the large size of its chromosomes.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.
Congenital absence of or defects in structures of the eye; may also be hereditary.
The female sex chromosome, being the differential sex chromosome carried by half the male gametes and all female gametes in human and other male-heterogametic species.
Proteins encoded by homeobox genes (GENES, HOMEOBOX) that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. Homeodomain proteins are involved in the control of gene expression during morphogenesis and development (GENE EXPRESSION REGULATION, DEVELOPMENTAL).
Deoxyribonucleic acid that makes up the genetic material of bacteria.
Elements of limited time intervals, contributing to particular results or situations.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
The process of intracellular viral multiplication, consisting of the synthesis of PROTEINS; NUCLEIC ACIDS; and sometimes LIPIDS, and their assembly into a new infectious particle.
Individuals whose ancestral origins are in the southeastern and eastern areas of the Asian continent.
Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.
The presence of apparently similar characters for which the genetic evidence indicates that different genes or different genetic mechanisms are involved in different pedigrees. In clinical settings genetic heterogeneity refers to the presence of a variety of genetic defects which cause the same disease, often due to mutations at different loci on the same gene, a finding common to many human diseases including ALZHEIMER DISEASE; CYSTIC FIBROSIS; LIPOPROTEIN LIPASE DEFICIENCY, FAMILIAL; and POLYCYSTIC KIDNEY DISEASES. (Rieger, et al., Glossary of Genetics: Classical and Molecular, 5th ed; Segen, Dictionary of Modern Medicine, 1992)
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.
The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
The ability of microorganisms, especially bacteria, to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).
Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.
The analysis of a sequence such as a region of a chromosome, a haplotype, a gene, or an allele for its involvement in controlling the phenotype of a specific trait, metabolic pathway, or disease.
The transfer of bacterial DNA by phages from an infected bacterium to another bacterium. This also refers to the transfer of genes into eukaryotic cells by viruses. This naturally occurring process is routinely employed as a GENE TRANSFER TECHNIQUE.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
The loss of one allele at a specific locus, caused by a deletion mutation; or loss of a chromosome from a chromosome pair, resulting in abnormal HEMIZYGOSITY. It is detected when heterozygous markers for a locus appear monomorphic because one of the ALLELES was deleted.
Any codon that signals the termination of genetic translation (TRANSLATION, GENETIC). PEPTIDE TERMINATION FACTORS bind to the stop codon and trigger the hydrolysis of the aminoacyl bond connecting the completed polypeptide to the tRNA. Terminator codons do not specify amino acids.
The occurrence in an individual of two or more cell populations of different chromosomal constitutions, derived from a single ZYGOTE, as opposed to CHIMERISM in which the different cell populations are derived from more than one zygote.
Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.
Actual loss of portion of a chromosome.
A method (first developed by E.M. Southern) for detection of DNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.
Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.
Any of the processes by which cytoplasmic or intercellular factors influence the differential control of gene action in bacteria.
An antineoplastic agent with alkylating properties. It also acts as a mutagen by damaging DNA and is used experimentally for that effect.
Tumors or cancer of the LUNG.
The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.
A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology.
An infant during the first month after birth.
An essential amino acid that is physiologically active in the L-form.
Tumors or cancer of the human BREAST.
DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition.
A group of enzymes which catalyze the hydrolysis of ATP. The hydrolysis reaction is usually coupled with another function such as transporting Ca(2+) across a membrane. These enzymes may be dependent on Ca(2+), Mg(2+), anions, H+, or DNA.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
Abnormal development of cartilage and bone.
A social group consisting of parents or parent substitutes and children.
The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases IMMUNITY, and provides energy for muscle tissue, BRAIN, and the CENTRAL NERVOUS SYSTEM.
Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration.
An encapsulated lymphatic organ through which venous blood filters.
A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.
A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter.
Tumor suppressor genes located in the 5q21 region on the long arm of human chromosome 5. The mutation of these genes is associated with familial adenomatous polyposis (ADENOMATOUS POLYPOSIS COLI) and GARDNER SYNDROME, as well as some sporadic colorectal cancers.
The phosphoprotein encoded by the BRCA1 gene (GENE, BRCA1). In normal cells the BRCA1 protein is localized in the nucleus, whereas in the majority of breast cancer cell lines and in malignant pleural effusions from breast cancer patients, it is localized mainly in the cytoplasm. (Science 1995;270(5237):713,789-91)
Tumors or cancer of the COLON or the RECTUM or both. Risk factors for colorectal cancer include chronic ULCERATIVE COLITIS; FAMILIAL POLYPOSIS COLI; exposure to ASBESTOS; and irradiation of the CERVIX UTERI.
"Homozygous DNA ligase IV R278H mutation in mice leads to leaky SCID and represents a model for human LIG4 syndrome". ... "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine. "Entrez Gene: LIG4 ... Lig4 deficiency in the mouse causes a progressive loss of haematopoietic stem cells and bone marrow cellularity during aging. ... Mutation Research. 433 (1): 53-8. doi:10.1016/s0921-8777(98)00063-9. PMID 10047779. Mahaney BL, Hammel M, Meek K, Tainer JA, ...
X-SCID). Since γc specifically associates with JAK3, mutations in JAK3 also result in SCID. Deficiency of JAK3 blocks signaling ... Jak3 KO mice showed reduced expression of colonic villin, carbonic anhydrase, secretory mucin muc2, and increased basal colonic ... "Mutations in severe combined immune deficiency (SCID) due to JAK3 deficiency". Human Mutation. 18 (4): 255-63. doi:10.1002/humu ... Mutations that abrogate Jak3 functions cause an autosomal severe combined immunodeficiency disease (SCID) while activating Jak3 ...
By crossing SCID mice with mice carrying mutations in related genes, such as interleukin-2Rgamma, more efficient ... November 2002). "NOD/SCID/gamma(c)(null) mouse: an excellent recipient mouse model for engraftment of human cells". Blood. 100 ... of the immune system are compromised varies according to what other mutations the mice carry along with the SCID mutation. ... and an autosomal recessive form that is similar to the disease in Arabian horses and SCID mice. X-SCID in dogs is seen in ...
... and promising prophylactic in vivo antiretroviral activity in Hu-PBL-SCID mice as well as therapeutic anti-retroviral activity ... stampidine reversed the effects of HIV exposure on the host transcriptome regardless of NRTI-sensitivity or RT mutations of the ... At nanomolar concentrations that are 4-logs lower than those achieved at its non-toxic dose levels in mice, rats, cats, and ... as well as recombinant HIV clones containing common patterns of RT mutations responsible for NRTI resistance such as multiple ...
Hirschhorn R (1993). "Identification of two new missense mutations (R156C and S291L) in two ADA- SCID patients unusual for ... "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine. Wilson DK, Rudolph ... Some mutations in the gene for adenosine deaminase cause it not to be expressed. The resulting deficiency is one cause of ... Conversely, mutations causing this enzyme to be overexpressed are one cause of hemolytic anemia. There is some evidence that a ...
Some SCID mice are shown to reject skin grafts, so it has been proposed that this disease arises from a leaky mutation, meaning ... While HIV normally cannot infect mice, SCID mice have been used to study HIV. Prior to the use of humanized SCID mice, ape ... Some examples include SCID-hu Thy/Liv mice, which are given human fetal thymus and liver cells, hu-SRC-SCID mice, which are ... NOD/SCID IL2Rγ mice have also been used to study human melanoma. SCID mice can serve many functions in research, particularly ...
2008). "A new Hu-PBL model for the study of human islet alloreactivity based on NOD-scid mice bearing a targeted mutation in ... The NSG mouse (NOD scid gamma mouse) is a brand of immunodeficient laboratory mice, developed and marketed by Jackson ... Fulop, GM; Phillips, RA (1990). "The Scid Mutation in Mice Causes a General Defect in DNA Repair". Nature. 347 (6292): 479-482 ... Mice homozygous for the mutation have severely reduced numbers of mature T and B cells. The phenotypic penetrance of Prkdcscid ...
The next big step in the development of humanized mice models came with transfer of the scid mutation to a non-obese diabetic ... The discovery of the athymic mouse, commonly known as the nude mouse, and that of the SCID mouse were major events that paved ... The first such mouse model was derived by backcrossing C57BL/Ka and BALB/c mice, featuring a loss of function mutation in the ... This resulted in the creation of the NOD-scid mice which lacked T cells, B cells, and NK cells. This mouse model permitted for ...
A strain of laboratory mouse, XID, is used to study XLA. These mice have a mutated version of the mouse Btk gene, and exhibit a ... A mutation occurs at the Bruton's tyrosine kinase (Btk) gene that leads to a severe block in B cell development (at the pre-B ... XLA was also historically mistaken as Severe Combined Immunodeficiency (SCID), a much more severe immune deficiency ("Bubble ... The rest of the cases occur as random mutations. If a carrier female gives birth to a male child, there is a 50% chance that ...
SCID) due to defective V(D)J recombination. Loss-of-function mutations in Artemis also cause SCID, but these patients do not ... All NHEJ mutant mice show a SCID phenotype, sensitivity to ionizing radiation, and neuronal apoptosis. A system was developed ... Hypomorphic mutations in LIG4 and XLF cause LIG4 syndrome and XLF-SCID, respectively. These syndromes share many features ... NHEJ efficiency could be compared across tissues of the same mouse and in mice of different age. Efficiency was higher in the ...
Mice take a brief time to reach sexual maturity. Mice have large litter sizes. The availability of hundreds of mutations ... Brain The specific immunodeficient mice that were used were the NOD/SCID mouse (non-obese diabetic/severe conditional ... Mammary cancers in mice can be caused by genetic mutations that have been identified in human cancer. This means models can be ... of the human and mouse genomes are syntenic. 40% of both human and mouse genomes can be aligned at the nucleotide level. Mice ...
... are first tested in mouse models of SMA created through a variety of mutations in the mouse SMN1 gene. If the mice show ... Valproic scid. Valproic acid in mice studies restored histone acetylation levels, increased levels of pro-survival factors, and ... Tested on: mouse (M), only mouse cells (MC), human (H), Drosophila (D), rat (R). Successful treatment: yes (y), yes but with ... Sodium butyrate was the first HDAC inhibitor tested in SMA mouse models. It prolonged SMA mouse life span by 35% and showed ...
January 2007). "WHIM syndrome myelokathexis reproduced in the NOD/SCID mouse xenotransplant model engrafted with healthy human ... May 2003). "Mutations in the chemokine receptor gene CXCR4 are associated with WHIM syndrome, a combined immunodeficiency ... WHIM syndrome results from autosomal dominant mutations in the gene for the chemokine receptor, CXCR4, resulting in a carboxy- ... As WHIM syndrome is a molecular disease arising from gain-of-function mutations in CXCR4, preclinical studies identified ...
... which is the causative gene of the scid mutation Lack of NK cells, dendritic cell dysfunctions, and other unknown deficiencies ... Cancer Infectious Diseases Regenerative Medicine Hematology Humanized mouse Nude mouse SCID mouse M. Ito and, et al. (2002). " ... such as nude mouse and NOD/scid mouse. Thus, the mouse can be the best model as a highly efficient recipient of human cells to ... A NOG (NOD/Shi-scid/IL-2Rγnull) mouse is a new generation of severely immunodeficient mouse, developed by Central Institute for ...
Severe combined immunodeficiency (SCID) mice, with an almost completely defective immune system FVB mice, whose large litter ... mice, with unusual regenerative capacities Waltzing mice, which walk in a circular pattern due to a mutation adversely ... The laboratory mouse genome has been sequenced and many mouse genes have human homologues. Other mouse species sometimes used ... "Researchers add mice to list of creatures that sing in the presence of mates"-Study of male mouse "song" with mouse song ...
... is closely connected with immune regulation and for so its mutation can lead to a SCID phenotype. This so-called ... The mouse analogue is called Rit1 or Bcl11b and is located on mouse chromosome 12. This gene encodes a C2H2-type zinc finger ... The symptoms of SCID caused by BCL11B mutation - apart from immunity defects - typically include teeth abnormalities, ... February 2003). "Homozygous deletions and point mutations of the Rit1/Bcl11b gene in gamma-ray induced mouse thymic lymphomas ...
Therefore, mutations of RAG2 gene can result in severe immune disorders such as SCID (Severe Combined Immunodeficiency) or ... This mice strain has an inactivated RAG2 gene, therefore homozygous mice are unable to initiate V(D)J rearrangement and ... Also, the RAG2 mutation can be combined with other mutations in order to develop further models useful for basic immunology ... In 1992, a RAG2 knockout mice strain was generated. Since then, it became a widely used mouse model in immunological research. ...
These mice are an important model of primary T cell deficiency. Severe combined immunodeficiency syndromes (SCID) are group of ... Loss of the thymus at an early age through genetic mutation (as in DiGeorge Syndrome) results in severe immunodeficiency and ... A fully functional thymus derived from reprogrammed mouse embryonic fibroblasts has been grown in the kidney capsule of mice. ... In mice, the nude mouse strain are congenitally thymic deficient. ...
Experiments in animal models have shown X-SCID to occur similarly in dogs, but not in mice. Alterations in the immune response ... SCID). Most of these mutations involve changes in one or a few nucleotides (DNA building blocks) in the gene. These changes ... "Detection of three nonsense mutations and one missense mutation in the interleukin-2 receptor gamma chain gene in SCIDX1 that ... "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine. Russell SM, Keegan ...
Sanchez JJ, Monaghan G, Børsting C, Norbury G, Morling N, Gaspar HB (May 2007). "Carrier frequency of a nonsense mutation in ... Ullman B, Gudas LJ, Cohen A, Martin DW (June 1978). "Deoxyadenosine metabolism and cytotoxicity in cultured mouse T lymphoma ... the adenosine deaminase (ADA) gene implies a high incidence of ADA-deficient severe combined immunodeficiency (SCID) in Somalia ... "Gene Therapy Rescues Cardiac Dysfunction in Duchenne Muscular Dystrophy Mice by Elevating Cardiomyocyte Deoxy-Adenosine ...
Zhou, G. (2014). "Humanized NOD-SCID IL2rg(-/-) mice as a preclinical model for cancer research and its potential use for ... 3 shows the output of a search for PDX models whose engrafted tumors have amplified KRAS, the TP53 A159V mutation, a deletion ... The Mouse Models of Human Cancer database (MMHCdb) is a unique, comprehensive online knowledgebase of mouse models of human ... Bult, C.J. (Jan 2015). "Mouse Tumor Biology (MTB): a database of mouse models for human cancer". Nucleic Acids Research. 43 (D1 ...
Furthermore, LEKTI-knockout mice exhibit a phenotype similar to Netherton syndrome in humans. There is no known cure at the ... Netherton syndrome is a severe, autosomal recessive form of ichthyosis associated with mutations in the SPINK5 gene. It is ... but are not as vulnerable to opportunistic pathogens as patients with true Natural Killer cell deficiency-type SCID. Netherton ... Complete SPINK5 gene deletions have been linked to severe cases, while mutations which induce alternate splicing or create ...
... SCID is caused by a mutation is the ZAP70 gene, which is involved in the development of T cells. It is ... 2002). "Reconstitution of lymphoid development and function in ZAP-70-deficient mice following gene transfer into bone marrow ... Hematopoietic stem cell transplantation is the only known cure for ZAP70 deficient SCID. ZAP70 deficiency SCID is estimated to ... ZAP70 deficiency, or ZAP70 deficient SCID, is a rare autosomal recessive form of severe combined immunodeficiency (SCID) ...
"Radiosensitive SCID patients with Artemis gene mutations show a complete B-cell differentiation arrest at the pre-B-cell ... "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine. Moshous D, ... SCID). Artemis was first identified as the gene defective in a subset of SCID patients that were unusually sensitive to ... Li L, Moshous D, Zhou Y, Wang J, Xie G, Salido E, Hu D, de Villartay JP, Cowan MJ (2002). "A founder mutation in Artemis, an ...
... inhibits epithelial-mesenchymal transition and human prostate cancer stem cell growth in NOD/SCID IL2Rγ null mice by regulating ... Mutations in the PTCH1 gene can lead to the abnormal activation of GLI transcriptional activity which in turn promotes tumor ... Identification of mutations in the human PATCHED gene in sporadic basal cell carcinomas and in patients with the basal cell ... 5E1 also restricts the proliferation of pancreatic cancer cells in mice. While shown to be effective in the lab, both these Shh ...
"Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID)". Nature. 377 (6544): 65-8. doi: ... Studies of the mouse counterpart suggest that this gene may be involved in the development of urogenital tract and female ... The mutations in this gene may lead to, but not a frequent cause of, cryptorchidism. GRCh38: Ensembl release 89: ... "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine. Burkhardt E, Adham ...
The loss of function mutation of Orai1 causes severe combined immunodeficiency (SCID) in humans The mammalian orai family has ... "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine. Feske S, Gwack Y, ... Prakriya M, Srikanth S, Puppel SH, Tanasa B, Hogan PG, Lewis RS, Daly M, Rao A (May 2006). "A mutation in Orai1 causes immune ...
SCID). Weak (hypomorphic) mutations in CARD11 causes atopic dermatitis disease. Gain-of-function mutations in CARD11 can result ... A common theme for all four CARD-CC family proteins in mice and humans is that they are activated by different protein kinase C ... Gain-of-function mutations in CARD14 results in psoriasis or PRP. There are indications that loss-of-function mutations in ... Loss-of-function mutations in CARD9 disrupts lectin receptor signaling like Dectin 1, which causes enhanced susceptibility to ...
For example, studies in mice bearing human skin grafts found a reduction in the size of lesions from psoriasis after treatment ... "Proteasome inhibition reduces superantigen-mediated T cell activation and the severity of psoriasis in a SCID-hu model". The ... are mediated mainly by salt bridges and hydrophobic interactions between conserved alpha helices whose disruption by mutation ...
"Overexpression of plasminogen activator inhibitor 2 in human melanoma cells inhibits spontaneous metastasis in scid/scid mice" ... The secretory signal peptide of PAI-2 is relatively inefficient, perhaps by evolutionary design, as various mutations to the ... "Mouse PubMed Reference:".. *^ Schroder WA, Major L, Suhrbier A (2011). "The role of SerpinB2 in immunity". Critical Reviews in ...
This group of T cells is much less common in humans and mice (about 2% of total T cells) and are found mostly in the gut mucosa ... Mutations of the FOXP3 gene can prevent regulatory T cell development, causing the fatal autoimmune disease IPEX. ... SCID), Omenn syndrome, and cartilage-hair hypoplasia.[46] Causes of partial insufficiencies of T cell function include acquired ... "Impaired CD8 T cell memory and CD4 T cell primary responses in IL-7Rα mutant mice". The Journal of Experimental Medicine. 204 ...
Capecchi MR (October 2001). "Generating mice with targeted mutations". Nature Medicine. 7 (10): 1086-90. doi:10.1038/nm1001- ... Fischer A, Hacein-Bey-Abina S, Cavazzana-Calvo M (June 2010). "20 years of gene therapy for SCID". Nature Immunology. 11 (6): ... More recently, mutation breeding has used exposure to chemicals or radiation to produce a high frequency of random mutations, ... "Knockout Mice". Nation Human Genome Research Institute. 2009.. *^ "GM pigs best bet for organ transplant". Medical News Today. ...
"DNA repair kinetics in SCID mice Sertoli cells and DNA-PKcs-deficient mouse embryonic fibroblasts". Chromosoma. 126 (2): 287- ... Inherited DNA repair gene mutations that increase cancer risk DNA repair gene Protein Repair pathways affected Cancers with ... Different mutations in ATM reduce HRR, SSA or NHEJ [48] leukemia, lymphoma, breast [48][49] ... mutations in RECQL4 cause Rothmund-Thomson syndrome, with alopecia, sparse eye brows and lashes, cataracts and osteoporosis[24] ...
SCID) mice, NOD-SCID mice, and recombination-activating gene 2 (Rag2)-knockout mice.[2] The mice used must be immunocompromised ... or KRAS/BRAF mutation status.[21] Due to their stability, the 27 colorectal PDX models may be able to serve as pre-clinical ... The NOD-SCID mouse is considered more immunodeficient than the nude mouse, and therefore is more commonly used for PDX models ... When the tumor-burden becomes too large for the F0 mouse, researchers passage the tumor over to the next generation of mice. ...
A strain of laboratory mouse, XID, is used to study XLA. These mice have a mutated version of the mouse Btk gene, and exhibit a ... A mutation occurs at the Bruton's tyrosine kinase (Btk) gene that leads to a severe block in B cell development (at the pre-B ... XLA was also historically mistaken as Severe Combined Immunodeficiency (SCID), a much more severe immune deficiency ("Bubble ... The rest of the cases occur as random mutations.[4] If a carrier female gives birth to a male child, there is a 50% chance that ...
The ovarian tissue may also be transplanted into mice that are immunocompromised (SCID mice) to avoid graft rejection, and ... Women with an inherited mutation in the DNA repair gene BRCA1 undergo menopause prematurely,[18] suggesting that naturally ... Titus et al.[19] showed that DNA double-strand breaks accumulate with age in humans and mice in primordial follicles. ... "Premature menopause in patients with BRCA1 gene mutation". Breast Cancer Res Treat. 100 (1): 59-63. doi:10.1007/s10549-006-9220 ...
Mutations of the FOXP3 gene can prevent regulatory T cell development, causing the fatal autoimmune disease IPEX. ... This group of T cells is much less common in humans and mice (about 2% of total T cells); and are found mostly in the gut ... SCID), Omenn syndrome, and cartilage-hair hypoplasia.[52] Causes of partial insufficiencies of T cell function include acquired ...
A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. „Nature". 367 (6464), s. 645-8, Feb 1994 ... DNMT3A mutations in acute myeloid leukemia. „N Engl J Med". 363 (25), s. 2424-33, Dec 2010. DOI: 10.1056/NEJMoa1005143. PMID: ... Myeloid malignancies: mutations, models and management. „BMC Cancer". 12, s. 304, 2012. DOI: 10.1186/1471-2407-12-304. PMID: ... Ras gene mutations in patients with acute myeloid leukaemia and exposure to chemical agents.. „Carcinogenesis". 25 (5), s. 749- ...
Severe combined immunodeficiency (SCID) mice models demonstrate that these precursors may be transmitted to recipients with ... This results in the formation of GC, where antigen-activated B cells are trapped to undergo somatic mutation, positive and ... Deficit of this factor in mice leads to a state resembling systemic lupus erythematosus (SLE). Furthermore, mice lacking LT or ... In mice lacking B cells, or with blocked TNF-a and lymphotoxin (LT) production, cells with FDC phenotype are missing. In normal ...
However, in mice there is no increase in mutation in the brain with aging. Mice defective in a gene (Pms2) that ordinarily ... "DNA repair kinetics in SCID mice Sertoli cells and DNA-PKcs-deficient mouse embryonic fibroblasts". Chromosoma. 126 (2): 287- ... so that it sustains a 500-fold higher mutation burden than normal mice. These mice showed no clear features of rapidly ... A mutation cannot be recognized by enzymes once the base change is present in both DNA strands, and thus a mutation cannot be ...
Because of this, it is able to routinely and accurately model genetic diseases caused by subtle SNPs or point mutations that ... September 2009). "Efficient targeting of a SCID gene by an engineered single-chain homing endonuclease". Nucleic Acids Res. 37 ... in contrast to mouse ES cells, have low rates of HR. The technique has been widely adopted for use in engineering human cell ... March 2009). "PIK3CA mutations in colorectal cancer are associated with clinical resistance to EGFR-targeted monoclonal ...
Modifying the genes causing these congenital diseases (on those diagnosed to have mutations of the gene known to cause these ... has also shown to reduce Aβ deposits in a transgenic mouse model of Alzeimer's dementia. There is also research going on on ... or even genetic diseases such as SCID. Some gene therapies have already been developed or are being developed to correct these ... RPE65 mutation-induced blindness) and Novartis' Kymriah (Chimeric antigen receptor T cell therapy) are the FDA's first approved ...
These events can be organized into two classes: rare mutation detection and rare sequence detection. Rare mutation detection ... 2017). "Single Cell-Based Vector Tracing in Patients with ADA-SCID Treated with Stem Cell Gene Therapy". Molecular Therapy - ... 2015). "In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy". Science. 351 (6271): ... dPCR's ability to detect rare mutations may be of particular benefit in the clinic through the use of the liquid biopsy, a ...
... mice, rats, rabbits, pigs, cattle, and various types of mammalian cells. Zinc finger nucleases have also been used in a mouse ... The ZFN-encoding mRNA was injected into one-cell embryos and a high percentage of animals carried the desired mutations and ... September 2009). "Efficient targeting of a SCID gene by an engineered single-chain homing endonuclease". Nucleic Acids Res. 37 ... Similar research of using ZFNs to create specific mutations in zebrafish embryo has also been carried out by other research ...
RAG-2 deficient mice were chosen over other methods of inducting immunodeficiency (such as SCID mice) as an absence of these ... Cancer cells, through mutation, may actually have mutations in some of the proteins involved in antigen presentation, and as ... mice although levels of macrophages at the site of tumor challenge are similar to wild type mice. INOS −/− mice also show ... IFN-γ null mice showed virtually no immunity, while IL-4 null mice showed a 50% reduction when compared to immunised wild type ...
15 December - Scientists use a new form of gene therapy to partially reverse aging in mice. After six weeks of treatment, the ... 7 March - German researchers identify a specific gene mutation in humans that provides a 50 percent lower risk of suffering a ... "Strimvelis receives European marketing authorisation to treat very rare disease, ADA-SCID". GlaxoSmithKline. 27 May 2016. ... "Researchers watch in 3-D as neurons talk to each other in a living mouse brain". Science Daily. 1 November 2016. Retrieved 1 ...
... orthotopic growth and the production of bloody pleural effusion by human malignant pleural mesothelioma cells in SCID mice". ... Mutations in this gene are associated with lung cancer. GRCh38: Ensembl release 89: ENSG00000133454 - Ensembl, May 2017 GRCm38 ... "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine. Nishioka M, Kohno T ...
Functional defects in this protein may be associated with the pathogenesis of severe combined immunodeficiency (SCID). Several ... Knockout studies in mice suggest that blocking apoptosis is an essential function of this protein during differentiation and ... "Oncogenic IL7R gain-of-function mutations in childhood T-cell acute lymphoblastic leukemia". Nat. Genet. 43 (10): 932-9. doi: ...
C.B-17 severe combined immunodeficient (scid) mice carry the scid mutation and are severely deficient in both T cell- and B ... scid mutation in mice confers hypersensitivity to ionizing radiation and a deficiency in DNA double-strand break repair.. K A ... scid mutation in mice confers hypersensitivity to ionizing radiation and a deficiency in DNA double-strand break repair. ... scid mutation in mice confers hypersensitivity to ionizing radiation and a deficiency in DNA double-strand break repair. ...
The sensitivity of scid fibroblasts established from C.B17-scid/scid fetuses to the DNA-damaging agents bleomycin, ... The scid mutation in mice causes defects in the repair system for both double-strand DNA breaks and DNA cross-links Mutat Res. ... These findings indicate that the scid mutation in mice causes defects in repairing both double-strand DNA breaks and DNA cross- ... The sensitivity of scid fibroblasts established from C.B17-scid/scid fetuses to the DNA-damaging agents bleomycin, ...
Home , Biological Sciences home , Research , Profile , Publications , Correction of the classical scid mouse mutation by gene ... Correction of the classical scid mouse mutation by gene repair. / Abdul-Razak, Hayder. ... An ex vivo strategy to correct the classical scid mouse, a model of human DNA-dependent protein kinase catalytic subunit (DNA- ... ZFN- and template-mediated gene repair of the scid mutation was demonstrated via the incorporation of a selection cassette and/ ...
In this paper, we focus on the historical development and phenotypic descriptions of mouse models used to study prostate cancer ... The use of immunodeficient and genetically engineered mouse models that mimic the human disease has been crucial in validating ... Mice with an autosomal recessive SCID mutation were characterized in 1983 [56]. SCID mice are deficient in mature B and T cells ... Metastasis to the bone occurred at a higher rate in the NOD-SCID mice (13/20 mice) relative to SCID mice (5/19 mice) [61, 66]. ...
Mice, SCID * Mutation * Neurofibromin 1 / chemistry * Neurofibromin 1 / genetics* * Neurofibromin 1 / metabolism ...
Homozygosity for the severe combined immunodeficiency (scid) mutation results in a block in T- and B-lymphocyte development. An ... Thymomagenesis in the NOD-scid/scid mouse was associated with expression of an NOD mouse-unique endogenous ecotropic murine ... The nonobese diabetic scid mouse: model for spontaneous thymomagenesis associated with immunodeficiency.. M Prochazka, H R ... The nonobese diabetic scid mouse: model for spontaneous thymomagenesis associated with immunodeficiency. ...
The mice carry two mutations on the NOD/ShiLtJ genetic background; severe combined immune deficiency (,em,scid,/em,) and a ... www.jax.org/jax-mice-and-services/in-vivo-pharmacology/humanized-mice,Please click here to order our Humanized Mice,/a,. ... mutation is in the DNA repair complex protein ,em,Prkdc,/em, and renders the mice B and T cell deficient. The ,em,IL2rg,sup, ... The immunodeficient NSG mice enable research in human immune function, infectious disease, diabetes, oncology, and stem cell ...
... including immunodeficient mice such as the Fox Chase SCID Beige mouse, for use in basic research and nonclinical drug discovery ... Fox Chase SCID Beige Mouse Details. A congenic mouse that possesses both autosomal recessive mutations SCID (Prkdcscid) and ... Fox Chase SCID Beige Mouse Details. A congenic mouse that possesses both autosomal recessive mutations SCID (Prkdcscid) and ... Fox Chase SCID Beige Mouse Details. A congenic mouse that possesses both autosomal recessive mutations SCID (Prkdcscid) and ...
A severe combined immunodeficiency mutation in the mouse. Nature 301:527-530. ... Mice.SCID (C.B-17/Icr-scid/scid) mice and immunocompetent C.B-17 (C.B-17/Icr-+/+) mice were obtained from Japan CLEA Inc. ( ... As controls, SCID mice (n = 10), C.B-17 mice (n = 6), and A/J mice (n = 6) were mock inoculated with PBS. The mice were ... As controls, SCID mice (n = 6) and C.B-17 mice (n = 6) were mock inoculated with PBS. The SCID mice were observed for 60 days, ...
The Utilization of the scid Mutation in the Study of T Cell Development.- Transgenic Scid Mice With a Functionally Rearranged ... Studies Using Scid Mice.- Growth of Human Tumors in Immune-Deficient scid Mice and nude Mice. ... T Cell-Independent Macrophage Activation in Scid Mice.- Pneumocystis carinii Pneumonia in scid/scid Mice.- Immunobiology of ... Leaky Phenotypes.- T Cell Leakiness in Scid Mice.- Limited Clonal Diversity of Serum Immunoglobulin in Leaky Scid Mice.- ...
... scid) mutation and the beta2m null allele. They lack MHC class I, exhibit low NK cell activity, and support markedly elevated ... These mice are doubly homozygous for the severe combined immunodeficiency ( ... Mice homozygous for both the B2mtm1Unc and Prkdcscid (commonly referred to as scid) mutations on the NOD/ShiLtSz background are ... Frozen Mouse Embryo. NOD.Cg-Prkdc,scid, B2m,tm1Unc,/J. $2595.00. Frozen Mouse Embryo. NOD.Cg-Prkdc,scid, B2m,tm1Unc,/J. $ ...
Mutations in the Protein Phosphatase PPM1D are oncogenic in certain cancers including diffuse intrinsic pontine glioma (DIPG). ... and define a critical link between oncogenic driver mutations and NAD metabolism, which can be exploited for tumor-specific ... Here, the authors show that PPM1D mutations in DIPG induce the silencing of the nicotinic acid phosphoribosyltransferase gene ... and uncover a synthetic lethal interaction between PPM1D mutations and nicotinamide phosphoribosyltransferase (NAMPT) ...
We have produced mice homozygous for both the scid and beige mutations. By contrast with C.B-17 scid mice, BALB/c scid.beige ... The scid mutation occurred in the allotype congenic C.B-17 line, and up to 25% of C.B-17 scid mice spontaneously produce both T ... Homozygous scid/scid;beige/beige mice have low levels of spontaneous or neonatal T cell-induced B cell generation.. D E Mosier ... Homozygous scid/scid;beige/beige mice have low levels of spontaneous or neonatal T cell-induced B cell generation. ...
Publications] Igakura,T.et al: A null mutation in basigin,an immunoglobulin superfamily member,indicates its important roles ... Therefore, when transplanting the bone-barrow cells of nude (rnu/rnu) rat to the scid mouse (rat BMT scid mouse), the ... Then, this mouse falls into GVHD after several months of the rat thymus graft and dies. At the rat BMT scid mouse, neither GVHD ... scid/scid) mouse. However the thymus is equipped with the normal organization. ...
Editing of the human genome to correct disease-causing mutations is a promising approach for the treatment of genetic disorders ... In a proof-of-principle experiment, ZFNs delivered to the liver in a mouse model of haemophilia B achieved a level of gene ... Here we show that ZFNs are able to induce DSBs efficiently when delivered directly to mouse liver and that, when co-delivered ... The level of gene targeting achieved was sufficient to correct the prolonged clotting times in a mouse model of haemophilia B, ...
Therefore, the scid mouse models may be useful for testing new chemotherapeutic agents against various human cancer types. ... CPA and doxorubicin improved survival in the HL60 leukemia model (P = 0.0018). Conclusions: These scid mouse human tumor models ... for growth in the scid mouse and the tumors response to conventional chemotherapeutic drugs. Methods: Established melanoma ( ... to reflect the clinical situation in that clinically active chemotherapeutic drugs are similarly active in the scid mouse ...
Knockout Tested Mouse monoclonal DNA PKcs antibody [18-2]. Validated in WB, IP, IHC, Inhibition, ICC/IF and tested in Rat, ... Hyper radiosensitivity of murine scid mutation, complementing 1 antibody. *Hyperradiosensitivity complementing 1, mouse, ... Secondary - Goat Anti-Mouse IgG H&L (HRP) (ab205719) WB, IP, ELISA, IHC-P ... Blots were developed with Goat anti-Mouse IgG H&L (IRDye® 800CW) preadsorbed ab216772 and Goat Anti-Rabbit IgG H&L (IRDye® ...
Hyper radiosensitivity of murine scid mutation, complementing 1 antibody. *Hyperradiosensitivity complementing 1, mouse, ... ab7291, a mouse anti-tubulin (1/1000) and ab150120, an Alexa Fluor® 594-conjugated goat anti-mouse IgG (1/1000) were also used. ... Control 1: primary antibody (1/500) and secondary antibody, ab150120, an Alexa Fluor® 594-conjugated goat anti-mouse IgG (1/ ... Oncotarget 8:43733-43751 (2017). ICC/IF ; Mouse . Read more (PubMed: 28415827) » ...
Monoclonal Anti-Interleukin-2 Soluble Receptor γ antibody produced in mouse for your research needs. Find product specific ... Mutation in IL2RG can leads to X-linked severe combined immunodeficiency (SCID) . Monoclonal anti-Interleukin-2 Soluble ... mouse cells transfected with human IL-2 soluble receptor γ. General description Interleukin-2 Receptor γ is a 64kD protein, ... Mouse anti-Interleukin-2 Soluble Receptor γ antibody reacts specifically with human IL-2 soluble receptor γ. The product has ...
Nude mice (6-week-old females; CLEA Japan) and NOD/SCID mice (6-week-old females; CLEA Japan) were used for the in vivo studies ... A, MEK1 Q56P mutation in the OCUM-1 cell line, MEK1 S72G mutation in the Okajima cell line, and KRAS G12V mutation in the HSC- ... Specifically, the MEK1 S72Q mutation in the Okajima cell line is a novel activating mutation, whereas the MEK1 Q56P mutation in ... whereas the MEK1 S72G mutation in the Okajima cell line is a novel mutation. This novel mutation was confirmed using the TOPO ...
Mutations in the p53 and SCID genes cooperate in tumorigenesis. Nacht, M., Strasser, A., Chan, Y.R., Harris, A.W., Schlissel, M ... Biological context of Mice, SCID. *These results suggest that the SCID-hu mouse provides a useful small animal model to assess ... High impact information on Mice, SCID. *The SCID-hu mouse is a heterochimeric small animal model designed to support ... scid mice [21].. *Significantly more of the HIV-1-infected SCID-hu mice expressed mRNA for human tumor necrosis factors alpha ...
Both NOG and NSG share the Prkdcscid mutation but differ in the IL2rg mutation. While NOG strain has a mutation in IL-2rg gene ... The first such error is in comparing huNOG-EXL mice to huNSG mice. Although the differences in NOG and NSG mice are likely ... The first such error is in comparing huNOG-EXL mice to huNSG mice. Although the differences in NOG and NSG mice are likely ... R/ We agree with the reviewer on the subtle difference between NOG and NSG mice. These strains harbor two mutations that make ...
2008). "A new Hu-PBL model for the study of human islet alloreactivity based on NOD-scid mice bearing a targeted mutation in ... The NSG mouse (NOD scid gamma mouse) is a brand of immunodeficient laboratory mice, developed and marketed by Jackson ... Fulop, GM; Phillips, RA (1990). "The Scid Mutation in Mice Causes a General Defect in DNA Repair". Nature. 347 (6292): 479-482 ... Mice homozygous for the mutation have severely reduced numbers of mature T and B cells. The phenotypic penetrance of Prkdcscid ...
Leaky scid phenotype associated with defective V(D)J coding end processing in Artemis-deficient mice. Mol. Cell. 2002. 10:1379- ... SCID (RS-SCID) condition. We presently report the occurrence of hypomorphic mutations of the Artemis gene in four patients from ... For example, many mutations in the Rag1 and Rag2 genes causing SCID have been analyzed in vitro and found to affect distinct ... Shin, EK, Perryman, LE, Meek, K. A kinase-negative mutation of DNA-PKCS in equine SCID results in defective coding and signal ...
Yes, forms tumors in nude or SCID mice. Comments The cell line exhibits a K-ras oncogene mutation at codon 12 where a GGT --, ...
The SCID mutation in mice causes a general defect in DNA repair. Nature. 1990;347:479-82. ... NOD/SCID/γ(c)(null) mouse: an excellent recipient mouse model for engraftment of human cells. Blood. 2002;100:3175-82. ... The first humanized mouse model was the severe combined immune-deficient (SCID) mouse lacking B and T cells (16,17). Then, ... This ZFN-treated HPSCs were capable of engraft in NOD-SCID IL2rγ-null mice and were able to produce a polyclonal multilineage ...
A, cell line-derived xenografts were grown subcutaneously in female SCID mice. Upon reaching 200 mm3, the mice were treated ... 7, 10), mutation or loss of PTEN ( 11), and activating mutations in the pleckstrin homology domain of Akt ( 12). ... It is noteworthy that an activating mutation in Raf in the HT-29-derived xenograft, together with a PIK3CA-activating mutation ... SCID) mice. Cell lines with H-Ras constructs were removed from G418 one passage before injection. When the tumors reached 200 ...
Fulop GM, Phillips RA: The SCID mutation in the mice causes a general defect in DNA repair. Nature 347:479-482, 1990Google ...
We screened for the scid mutation by the absence of both T-cells (CD3, 2C11; BD Bioscience) and B-cells (B220, RA3-6B2; BD ... Four types of scid mice were used as recipients: B6.scid, CB17.scid, NOD.scid, and NOD.scid/RIP-B7.1. In addition, irradiated ... B6.scid (□, n = 6), CB17.scid (⋄, n = 4), NOD.scid (▴, n = 8), and NOD.scid/RIP-B7.1 mice (▵, n = 10). B: Diabetic spleen cells ... B6.scid (□, n = 6), CB17.scid (⋄, n = 4), NOD.scid (○, n = 15), and NOD.scid/RIP-B7.1 mice (•, n = 15). Diabetes was monitored ...
Leaky scid phenotype associated with defective V(D)J coding end processing in Artemis-deficient mice. Mol Cell 2002;10:1379- ... RAG1-S723C knockin mice. Mice harboring the RAG1-S723C knockin mutation at the endogenous locus were generated via gene ... Inactivating mutations in RAG1 and RAG2 cause T−B− severe combined immunodeficiency (SCID) in human patients, whereas ... RAG1-S723C homozygous mice exhibit impaired lymphocyte development. The impact of the RAG1-S723C mutation on lymphocyte ...
  • NSG mice are deficient in mature lymphocytes, serum Ig is not detectable and natural killer (NK) cell cytotoxic activity is extremely low. (jax.org)
  • Growth Requirements of B Lineage Lymphocytes From Scid and Normal Mice. (wisepress.com)
  • Studies of HIV Infection and the Development of Epstein-Barr Virus-Related B Cell Lymphomas Following Transfer of Human Lymphocytes to Mice With Severe Combined Immunodeficiency. (wisepress.com)
  • Human Lung Tumors, Patients' Peripheral Blood Lymphocytes and Tumor Infiltrating Lymphocytes Propagated in Scid Mice. (wisepress.com)
  • Adoptive Transfer of Human Peripheral Blood Lymphocytes (PBL) in Scid Mice. (wisepress.com)
  • The SCID mutation results in severe combined immunodeficiency affecting both the B and T lymphocytes. (criver.com)
  • Therefore, when transplanting the bone-barrow cells of nude (rnu/rnu) rat to the scid mouse (rat BMT scid mouse), the lymphocytes of the donor origin immigrate into the thymus. (nii.ac.jp)
  • Prkdcscid is a loss-of-function mutation in the mouse homologue of the human PRKDC gene, which encodes a protein that resolves DNA strand breaks that occur during V(D)J recombination in developing T and B lymphocytes. (wikipedia.org)
  • An immunologist at the Fox Chase Cancer Center in Philadelphia, he was studying, in genetically defined strains of mice, the development of lymphocytes - white blood cells - especially the antibody-forming ones, called B cells. (calvin.edu)
  • Named scid mice (for "severe combined immunodeficiency"), the mutant mice lacked both B and T lymphocytes, cells that provide protection against harmful microbes and that are able to cause the rejection of foreign transplanted tissues. (calvin.edu)
  • What we found is that the scid mutation crippled a gene that lymphocytes use to make receptors that recognize anything foreign to the body. (calvin.edu)
  • To study the regulation of anti-self B lymphocytes, the Bosmas have engineered scid mice to produce B - but not T - lymphocytes that react to the body's own DNA. (calvin.edu)
  • The balance of lymphocytes and neutrophils in adult animals is quite different: human blood is neutrophil rich (50-70% neutrophils, 30-50% lymphocytes) whereas mouse blood has a strong preponderance of lymphocytes (75-90% lymphocytes, 10-25% neutrophils) ( 10 ). (jimmunol.org)
  • Transfer of peripheral lymph node lymphocytes to SCID mice leads to the long term establishment of mucosal T lymphocytes within the epithelium and lamina propria of the small and large intestines. (jimmunol.org)
  • Optimal engraftment of intestinal T cells required bacterial flora, as the number of lymphocytes was greatly reduced in SCID recipients with a reduced flora. (jimmunol.org)
  • The acquisition of phenotypic markers characteristic of the intestinal microenvironment by engrafted cells suggests that T cell migration of lymphocytes to the SCID intestine is not aberrant, but it may reflect processes that are ongoing in immunocompetent mice. (jimmunol.org)
  • RAG-1-deficient mice have no mature B and T lymphocytes. (nih.gov)
  • RAG-1-deficient mice have small lymphoid organs that do not contain mature B and T lymphocytes. (nih.gov)
  • To address this deficiency, we used mice harboring the severe combined immune deficiency (SCID) spontaneous mutation, which lack mature T and B lymphocytes and are unable to mount an acquired immune response. (aspetjournals.org)
  • The CB17-SCID mouse has quite active NK cells, and when the mice get older, T and B lymphocytes develop," says Leonard Shultz, who studies humanized mice as a professor at the Jackson Laboratory, a leading genetics research lab in Maine. (iavireport.org)
  • The severe immunodeficiency allows the mice to be humanized by engraftment of human CD34+ hematopoietic stem cells (HSC), peripheral blood mononuclear cells (PBMC), patient derived xenografts (PDX), or adult stem cells and tissues. (jax.org)
  • These mutant mice have been shown to readily support engraftment of human CD34 + hematopoietic stem cells and represent a superior, long-lived model suitable for studies employing xenotransplantation strategies. (jax.org)
  • 2016. Myeloid Engraftment in Humanized Mice: Impact of Granulocyte-Colony Stimulating Factor Treatment and Transgenic Mouse Strain. (jax.org)
  • V. Potential Uses: Engraftment with Syngeneic Mouse Cells. (wisepress.com)
  • 1997. Enhanced human CD4+ T cell engraftment in beta2-microglobulin-deficient NOD-scid mice. (jax.org)
  • Long-term engraftment of fresh human myeloma cells in SCID mice. (semanticscholar.org)
  • The compound immunodeficiencies in NSG branded mice permit the engraftment of a wide range of primary human cells, and enable sophisticated modeling of many areas of human biology and disease. (wikipedia.org)
  • Thus, there are now 3 variables that exist between the 2 main study groups: mouse background strain, inclusion of human knock-in genes, and route of human cell engraftment. (mdpi.com)
  • The addition of a targeted null mutation in the interleukin (IL)-2 receptor common γ-chain fully disrupts NK cell development, further reducing innate immune responses, and facilitating the engraftment of human cells and tissues ( 17 ). (diabetesjournals.org)
  • Engraftment of human HSCs in nonirradiated newborn NOD-scid IL2rγ null mice is enhanced by transgenic expression of membrane-bound human SCF. (semanticscholar.org)
  • Heightened levels of human HSC engraftment are observed in immunodeficient mice expressing mutations in the IL2-receptor common γ chain (IL2rg) gene, including NOD-scid IL2rγ(null) (NSG) mice. (semanticscholar.org)
  • Kit regulates HSC engraftment across the human-mouse species barrier. (semanticscholar.org)
  • Intra-bone marrow transplantation of human CD34(+) cells into NOD/LtSz-scid IL-2rgamma(null) mice permits multilineage engraftment without previous irradiation. (semanticscholar.org)
  • mouse: an excellent recipient mouse model for engraftment of human cells. (taconic.com)
  • To evaluate the usefulness of NR2G mice as a host for humanized mice, the engraftment rates and differentiation of human cells after human hematopoietic stem cell (HSC) transplantation were compared among NR2G, NOG, and NOD-scid mice. (jove.com)
  • These HSC transplantation experiments demonstrated that both NR2G and NOG mice showed high engraftment rates compared with NOD-scid mice, although NOG mice showed a slightly higher engraftment rate than that for NR2G mice. (jove.com)
  • The HSC transplantation experiments to adults and newborns of two immunodeficient mice also revealed that the HSC transplantation into newborn mice resulted in higher engraftment rate than those into adults. (jove.com)
  • Engraftment and Development of Human T and B Cells in Mice After Bone Marrow Transplantation", Reports, Apr. (patentgenius.com)
  • Engraftment of Immune-Deficient Mice with Human Hematopoietic Stem Cells", Science 242:1706 (1989). (patentgenius.com)
  • Successful Engraftment of Human Postnatal Thymus in Severe Combined Immune Deficient (SCID) Mice: Differential Engraftment of Thymic Components With Irradiation Versis Anti-asialo GM-1 Immuno-Suppressive Regimens", J. Exp. (patentgenius.com)
  • Moreover, as it is highly permissive to human hematopoietic cells engraftment, BRGSF serves as the optimal model to generate human immune system (HIS) mice to study and predict human immune responses in vivo . (genoway.com)
  • Similarly, the greatest engraftment of primary human acute myeloid leukemia samples was achieved in NSG-SGM3 mice followed by NOD/SCID-SGM3, NSG, and NOD/SCID. (bloodjournal.org)
  • These NOD-SCID mice supported better engraftment with human CD34+ hematopoietic stem cells (HSCs), the cells from which most other immune cells develop, for up to six months following transplantation, which is much longer than HSCs last in vitro , Manz says. (iavireport.org)
  • It was known that lower NK cell activity contributed to the increased ability of NOD-SCID mice to support human HSC engraftment, according to Shultz. (iavireport.org)
  • Functional NK cells may impact engraftment success of life-saving procedures such as bone marrow transplantation in human SCID patients. (bmbreports.org)
  • Transplantation assays performed in mice have proven invaluable for studying murine and human stem cell biology, facilitating an improved understanding of the immunophenotype, homing ability, engraftment properties, cytokine responsiveness and radiation sensitivity of repopulating cells. (stemcell.com)
  • 1, 2 Various assay formats have been developed that differ in the choice of donor and host mouse strains, the method to ablate or suppress host hematopoiesis prior to donor cell transplantation, the detection methods used to identify the progeny of donor-derived stem cells, and the endpoints and criteria for "successful" engraftment. (stemcell.com)
  • Heterozygotes were interbred to produce mice homozygous for the Prkdc scid allele and homozygous (females) or hemizygous (males) for the Il2rg tm1Wjl allele. (jax.org)
  • These mice are doubly homozygous for the severe combined immunodeficiency (scid) mutation and the beta2m null allele. (jax.org)
  • Mice homozygous for both the B2m tm1Unc and Prkdc scid (commonly referred to as scid ) mutations on the NOD/ShiLtSz background are class I deficient, B and T cell deficient, C-5 deficient ( Hc 0 ), and have low NK cells. (jax.org)
  • Homozygous scid/scid;beige/beige mice have low levels of spontaneous or neonatal T cell-induced B cell generation. (rupress.org)
  • We have produced mice homozygous for both the scid and beige mutations. (rupress.org)
  • Mice homozygous for the mutation have severely reduced numbers of mature T and B cells. (wikipedia.org)
  • RAG1-S723C homozygous mice exhibit impaired lymphocyte development and decreased V(D)J rearrangements. (bloodjournal.org)
  • Mice homozygous for the scid mutation lack both T and B cells due to a defect in V(D)J recombination. (taconic.com)
  • We have studied a mut/mut mouse model of leaky SCID with a homozygous Rag1 S723C mutation that impairs, but does not abrogate, V(D)J recombination activity. (scialert.net)
  • Charron J, Malynn BA, Fisher P, Stewart V, Jeannotte L, Goff SP, Robertson EJ, Alt FW (1992) Embryonic lethality in mice homozygous for a targeted disruption of the N-myc gene. (springer.com)
  • C.B-17 severe combined immunodeficient (scid) mice carry the scid mutation and are severely deficient in both T cell- and B cell-mediated immunity, apparently as a result of defective V(D)J joining of the immunoglobulin and T-cell receptor gene elements. (pnas.org)
  • The scid mutation is in the DNA repair complex protein Prkdc and renders the mice B and T cell deficient. (jax.org)
  • Thus was the C.B-17/Icr scid or severe combined immune deficient (scid) mouse discovered. (wisepress.com)
  • Establishment of Assays for Human Hematopoietic Cells in Immune Deficient Mice. (wisepress.com)
  • Growth of Human Tumors in Immune-Deficient scid Mice and nude Mice. (wisepress.com)
  • NSG branded mice are also deficient in multiple cytokine signaling pathways, and they have many defects in innate immunity. (wikipedia.org)
  • T cell development in E2A-deficient mice is partially arrested before lineage commitment. (rupress.org)
  • B cell development in E2A- and E47-deficient mice is completely arrested before Ig gene rearrangement ( 4 )( 5 )( 6 ). (rupress.org)
  • Thymuses from E47-deficient mice are markedly hypocellular due to defects preceding T-lineage commitment and the initiation of TCR gene rearrangements ( 7 ). (rupress.org)
  • Although RAG-1 expression has been reported in the central nervous system of the mouse, no obvious neuroanatomical or behavioral abnormalities have been found in the RAG-1-deficient mice. (nih.gov)
  • This enables p53-deficient tumor cells with DNA damage to continue cycling, creating a permissive environment for the acquisition of additional mutations. (aacrjournals.org)
  • The loss of checkpoint control enables p53-deficient tumors to continue cycling, creating a permissive environment for the acquisition of additional mutations. (aacrjournals.org)
  • A Model Human Acute Lymphoblastic Leukemia in Immune-Deficient SCID Mice", Science 246:1597 (1989). (patentgenius.com)
  • The elimination of this activity in SYCP3- or SYCP2-deficient oocytes may underlie the aneuploidy in derivative mouse embryos and spontaneous abortions in women. (genetics.org)
  • In order to bridge this gap and enhance the transfer of knowledge from in vitro and mouse-based investigations toward clinical applications, scientists have generated a wide variety of immunodeficient models such as SCID, NUDE and Rag-deficient mice engrafted either subcutaneously or orthotopically with cell-derived xenografts (CDXs) or patient-derived xenografts (PDXs). (genoway.com)
  • SCID and Rag-deficient mice, on the other hand, were the perfect hosts to study blood cancers such as lymphoma, myeloma, and leukemia, as they are more immunodeficient (i.e., they both lack T and B cells) than NUDE mice. (genoway.com)
  • For all these reasons, scientists developed a new generation of highly immunodeficient mice by backcrossing SCID and Rag-deficient mice into non-obese diabetic (NOD) or Balb/c mice. (genoway.com)
  • Reversible defects in natural killer and memory CD8 T cell lineages in interleukin 15-deficient mice. (springer.com)
  • JAK1 deficient mice shows severely impaired thymic development and no hematopoietic colony formation in response to IL-7. (wikipathways.org)
  • 1997). Base transitions dominate the mutational spectrum of a transgenic reporter gene in MSH2 deficient mice. (ubc.ca)
  • Chen J, Trounstine M, Alt FW, Young F, Kurahara C, Loring JF, Huszar D (1993a) Immunoglobulin gene rearrangement in B cell deficient mice generated by targeted deletion of the JH locus. (springer.com)
  • The first SCID/BLAJ mouse model of dysferlinopathy was created by Dr. Ivan Torrente by backcrossing dysferlin deficient BLA/J mice onto the SCID strain while selecting for the retrotransposon insertion in intron 4 of the dysferlin gene, as well as the absence of specific B- and T- lymphocyte markers (CD4, CD8, and CD19) in cells isolated from peripheral blood. (jain-foundation.org)
  • In this study we demonstrate that whenever a fraction of mouse or human adult bone marrow-derived stem cells (lineage-negative hematopoietic stem cells [Lin - HSCs]) containing endothelial precursors stabilizes and rescues retinal blood vessels that would ordinarily completely degenerate, a dramatic neurotrophic rescue effect is also observed. (jci.org)
  • In order to investigate the dynamics of human-specific pathogens in vivo , we have recently constructed a humanized mouse (NOG-hCD34 mouse) model by xenotransplanting human CD34 + hematopoietic stem cells into an immunodeficient NOD/SCID/IL-2R-γ null (NOG) mouse ( 15 , 34 ). (asm.org)
  • The human immune system can be reconstituted in experimental animals by transplanting human hematopoietic stem cells (hHSCs) into immunodeficient mice. (jove.com)
  • The NOD/Nju carries a mutation in the Sirpa ( SIRP α ) gene that allows for engrafting of foreign hematopoietic stem cells. (hemacare.com)
  • In scid haematopoietic progenitors, gene correction was demonstrated only when the ZFN genes were delivered by integrating lentiviral vectors. (royalholloway.ac.uk)
  • Rearrangement of T Cell Receptor Delta Genes in Thymus of Scid Mice. (wisepress.com)
  • Human-specific gene expression profiles in grafts from infected mice revealed the induction of multiple interferon-stimulated genes. (diabetesjournals.org)
  • outlines a general screening strategy for the discovery of clinically relevant mutations in cancer genes, and shows how in silico technologies can accelerate drug discovery in the absence of a crystal structure of a protein-drug complex. (elifesciences.org)
  • This conservation of function is reflected in recent reports on the sequencing of both the human and mice genomes, which reveal that to date only 300 or so genes appear to be unique to one species or the other ( 1 ). (jimmunol.org)
  • Hypomorphic mutations in genes that control T cell development have been associated with immunodeficiency and immune dysregulation both in humans and in mice. (frontiersin.org)
  • We have studied T cell development and thymic stroma architecture and maturation in two mouse models of leaky severe combined immune deficiency, carrying hypomorphic mutations in rag1 and lig4 genes. (frontiersin.org)
  • Substitution of the structural genes of dengue virus type 4 with those of type 2 results in chimeric vaccine candidates which are attenuated for mosquitoes, mice, and rhesus monkeys. (nih.gov)
  • To explore this concept, we assessed the immunogenicity of a panel of genes that are common sites of driver mutations in follicular lymphoma, an immunologically sensitive yet currently incurable disease. (aacrjournals.org)
  • Exon capture and NGS were used to interrogate tumor samples from 53 patients with follicular lymphoma for mutations in 10 frequently mutated genes. (aacrjournals.org)
  • Mutations were identified in 1-5 genes in 81% (43/53) of tumor samples. (aacrjournals.org)
  • We applied a previously described 17-gene expression score comprising genes differently expressed between LSC and leukemic bulk blasts, for 934 adult patients with de novo AML, and studied associations of the 17-gene LSC score with clinical data and mutation status of 81 genes recurrently mutated in cancer and leukemia. (haematologica.org)
  • Rearrangement of Antigen Receptor Genes Is Defective in Mice with Severe Combined Immune Deficiency", Cell 46:963-972 (1986). (patentgenius.com)
  • Nucleotide sequencing of the premembrane (prM) and envelope (E) structural protein genes of this strain, TM171-03, and comparison with sequences from other North American isolates indicated that this virus had accumulated several unique mutations from the New York 1999 strain 382-99 (NY99) prototype sequence. (cdc.gov)
  • As reported previously, sequencing the prM-E genes of TM171-03 (V1 passage) identified nonsynonymous mutations encoding substitutions at prM-141 Ile→Thr and E156 Ser→Pro ( 2 ). (cdc.gov)
  • Acute myeloid leukemia (AML) is associated with mutations or chromosomal translocations in genes encoding transcription factors. (uwo.ca)
  • Blackwell TK, Malynn BA, Pollock RR, Ferrier P, Covey L, Fulop GM, Phillips RA, Yancopoulos GD, Alt FW (1989) Isolation of scid pre-B cells that rearrange kappa light chain genes: formation of normal signal and abnormal coding joins. (springer.com)
  • Chen J, Trounstine M, Kurahara C, Young F, Kuo C-C, Xu Y, Loring JF, Alt FW, Huszar D (1993b) B cell development in mice that lack one or both immunoglobulin k light chain genes. (springer.com)
  • SCID is a group of rare congenital syndromes caused by mutations in genes responsible for the development of both T and B cells. (bmbreports.org)
  • So far, mutation(s) in more than 30 genes that might cause SCID have been discovered. (bmbreports.org)
  • SCID pig models depict numerous types of immune cell profiles due to defects in different signaling pathways and mutations in different genes. (bmbreports.org)
  • Purpose: To test a number of established human tumor cell lines and early passage breast cancer (UACC2150) and melanoma cells (UACC1273) for growth in the scid mouse and the tumors' response to conventional chemotherapeutic drugs. (semanticscholar.org)
  • Overall, our results reveal a promising approach for the targeting of PPM1D mutant tumors, and define a critical link between oncogenic driver mutations and NAD metabolism, which can be exploited for tumor-specific cell killing. (nature.com)
  • Tumor-promoting barbiturates act on DNA repair of cultured hepatocytes, Mutation Research Letters, Elsevier, vol. 173, No. 2, pp. 147-152 (1986). (freepatentsonline.com)
  • Most importantly, 1-(2-hydroxy-4-morpholin-4-yl-phenyl)-ethanone synergistically enhances radiation-induced tumor control in a mouse-human xenograft assay. (aacrjournals.org)
  • The two DEN2/4 chimeric viruses lacking the delta 30 mutation were highly attenuated in tumor-bearing SCID-HuH-7 mice, mosquitoes, and rhesus monkeys, indicating chimerization with either the CME or ME regions lead to attenuation. (nih.gov)
  • 2003. Paclitaxel encapsulated in cationic liposomes diminishes tumor angiogenesis and melanoma growth in a 'humanized' SCID mouse model. (meduniwien.ac.at)
  • UV-induced mutations of the tumor suppressor gene TP53 are of major importance in the development of actinic keratosis. (medscape.com)
  • Here, we review the evidence supporting a role for p53 loss or mutation in tumor metastasis, with an emphasis on breast cancer. (aacrjournals.org)
  • Understanding the mechanisms by which p53 loss and mutation promote tumor metastasis is crucial to understanding the biology of tumor progression and how to appropriately apply targeted therapies. (aacrjournals.org)
  • The ability of a tumor cell to undergo this full metastatic program is thought to require a plethora of somatic mutations and changes in gene expression and metabolism that allow it to successfully complete each step. (aacrjournals.org)
  • 1,2 Syngeneic tumor transplantation and genetically engineered mouse models have offered tremendous insight in the basic mechanisms of immune regulation. (genoway.com)
  • Anti-tumor efficacy studies using gefitinib demonstrated that the EGFR activating mutation model had superior sensitivity and that the KRAS mutation models were resistant to gefitinib. (biomedcentral.com)
  • Gefitinib anti-tumor efficacy in these patient-derived NSCLC xenografts containing EGFR and KRAS mutation was consistent with the reported results from previous clinical trials. (biomedcentral.com)
  • severe combined immune deficiency ( scid ) and a complete null allele of the IL2 receptor common gamma chain ( IL2rg null ). (jax.org)
  • The IL2rg null mutation prevents cytokine signaling through multiple receptors, leading to a deficiency in functional NK cells. (jax.org)
  • The NOD.Cg- Prkdc scid Il2rg tm1Wjl /SzJ mice, most often known by their branded name, NOD scid gamma (NSG™), do not express the Prkdc gene nor the X-linked Il2rg gene. (jax.org)
  • These double mutant mice were produced by breeding female NOD.CB17- Prkdc scid /J (Stock No. 001303 ) mice with male mice bearing the X-linked B6.129S4- Il2rg tm1Wjl /J allele (Stock No. 003174 ). (jax.org)
  • The resulting male mice heterozygous for the Prkdc scid allele and hemizygous for the Il2rg tm1Wjl allele were crossed to female NOD.CB17- Prkdc scid /J (Stock No. 001303 ) mice for eight generations. (jax.org)
  • The Il2rgtm1Wjl targeted mutationb is a complete null mutation in the gene encoding the interleukin 2 receptor gamma chain (IL2Rγ, homologous to IL2RG in humans). (wikipedia.org)
  • Given these inherent limitations, we used the NOD/Lt- Prkdc scid IL2rg tm1WJL (NSG) mouse ( 14 ) to study the effects of CVB infection in transplanted human islets. (diabetesjournals.org)
  • The Il2rg targeted mutation was developed by Dr. Kazuo Sugamura of Tohoku University by targeting the gene in ES cells derived from a 129 strain. (taconic.com)
  • The CIEA NOG mouse ® was developed by backcrossing the C57BL/6JJic-Il2rg line to the NOD/ShiJic-Prkdc scid line for a total of eight generations. (taconic.com)
  • The transgenic hIL6- NOD/Shi-IL2rg mouse was crossed on to the NOG background to introduce the Prkdc scid mutation. (taconic.com)
  • Correction of murine SCID-X1 by lentiviral gene therapy using a codon-optimized IL2RG gene and minimal pretransplant conditioning. (southernbiotech.com)
  • This humanized mouse model was created by sequential CRISPR/Cas9 editing of the Prkdc and Il2rg loci in the NOD/Nju mouse, generating a mouse coisogenic to the NOD/Nju. (hemacare.com)
  • The knockout of the Il2rg gene further exacerbates the SCID-like phenotype while additionally resulting in a decrease of NK cell production. (hemacare.com)
  • Results Arrests in T-cell development caused by mutations in IL-7 receptor α (IL7RA) and IL-2 receptor γ (IL2RG) were observed at the most immature thymocytes much earlier than expected based on gene expression profiling of human thymocyte subsets and studies with corresponding mouse mutants. (eur.nl)
  • We propose that the unusual features of T-cell ontogeny characteristic of the NOD inbred strain synergize with the scid-imparted block in thymocyte development, leading to activation of the NOD-unique Emv-30 to initiate thymomagenesis. (pnas.org)
  • The phenotypic penetrance of Prkdcscid varies among inbred strain backgrounds, but the mutation is most effective at eliminating adaptive immunity on the NOD genetic background. (wikipedia.org)
  • Bone marrow stem cells, intestinal crypt cells, and epithelial skin cells from scid mice are 2- to 3-fold more sensitive when irradiated in situ than are congenic BALB/c or C.B-17 controls. (pnas.org)
  • The severe combined immunodeficient (SCID) mouse has no functional T and B cells ( 6 , 8 ). (asm.org)
  • Natural Killer Cells and Their Precursors in Mice With Severe Combined Immunodeficiency. (wisepress.com)
  • Reconstitution of Scid Mice by Injection of Varying Numbers of Normal Fetal Liver Cells into Scid Neonates. (wisepress.com)
  • The Scid Mouse as a Model to Identify and Quantify Myeloid and Lymphoid Stem Cells. (wisepress.com)
  • The beige mutation results in defective natural killer (NK) cells. (criver.com)
  • The scid mutation occurred in the allotype congenic C.B-17 line, and up to 25% of C.B-17 scid mice spontaneously produce both T cells and immunoglobulin, a phenotype known as "leaky. (rupress.org)
  • Moreover, introduction of neonatal T cells into C.B-17 scid mice leads to immunoglobulin production by 100% of animals. (rupress.org)
  • Because the lymphocyte stem cell has a malfunction, no population of both T and B cells exists in the lymphoid organs of scid (scid/scid) mouse. (nii.ac.jp)
  • This phenomenon is peculiar, because both the expression patterns of TCR of T cells and IgG of B cells in rat BMT scid mouse are as those of normal rat. (nii.ac.jp)
  • When injecting the spleen cells of the rat BMT scid mouse into nude rat, the decrease of the weight is remarkable from 3 months to 5 months after the treatment and the GVHD-like disease occurred. (nii.ac.jp)
  • Successful transfer of localized autoimmunity with positively selected CD4^+ cells to scid mice lacking functional B cells'Autoimmunity. (nii.ac.jp)
  • Dual effects of human adipose tissue-derived mesenchymal stem cells in human lung adenocarcinoma A549 xenografts and colorectal adenocarcinoma HT-29 xenografts in mice. (semanticscholar.org)
  • Gene-specific targeting has historically been limited to mouse embryonic stem cells. (nature.com)
  • NSG branded mice lack mature T cells, B cells, and natural killer (NK) cells. (wikipedia.org)
  • 2005). "Human lymphoid and myeloid cell development in NOD/LtSz-scid IL2R gamma null mice engrafted with mobilized human hemopoietic stem cells" (PDF). (wikipedia.org)
  • mouse cells transfected with human IL-2 soluble receptor γ. (sigmaaldrich.com)
  • The identification of additional oncogenes with influences similar to those of epidermal growth factor receptor gene mutations, upon which the growth of cancer cells is dependent, is needed. (aacrjournals.org)
  • Considering the addiction of cancer cells to active MEK1 mutations for proliferation, gastric cancer with such oncogenic MEK1 mutations might be suitable for targeted therapy with MEK inhibitors. (aacrjournals.org)
  • Therefore, the identification of additional oncogenes with effects similar to those of EGFR mutations or anaplastic lymphoma kinase ( ALK ) gene rearrangements and upon which cancer cells are dependent is needed ( 13 ). (aacrjournals.org)
  • In addition, the Methods indicate that NOG-EXL mice were engrafted via tail vein injection and NSG mice were engrafted via intrahepatic injection of human cells. (mdpi.com)
  • If different donors were used for the different mouse strains, that can also affect the results because not all donor cells engraft with equal efficiency into immunodeficient mice, depending upon the donor genotype. (mdpi.com)
  • Immune tolerance can be broken in these diabetes-resistant mice expressing H-2 g7 if the costimulatory molecule B7.1 is present on the islet β cells. (diabetesjournals.org)
  • Hyperglycemia was induced in mice by specific ablation of native β-cells. (diabetesjournals.org)
  • NOD mice have been used to extensively assess the parameters of viral infection on T1D, although a critical mass of autoreactive T cells rather than direct viral insult appears to accelerate progression to diabetes during CVB infection ( 12 , 13 ). (diabetesjournals.org)
  • Lig4 deficiency in the mouse causes a progressive loss of haematopoietic stem cells and bone marrow cellularity during aging. (wikipedia.org)
  • designed a new screening method in human prostate cancer cells and showed that androgen receptors with a specific mutation (called F876L) can be activated by enzalutamide. (elifesciences.org)
  • More comprehensive biological studies showed that prostate cancer cells harboring the mutation continued to grow when treated with the drug. (elifesciences.org)
  • also showed that this mutation can arise spontaneously in human prostate cancer cells treated long term with enzalutamide. (elifesciences.org)
  • Tyrosine kinase receptor expression on putative hemopoietic stem cells (HSC) 2 shows a reciprocal pattern, with mouse HSC being predominantly c- kit high , flt-3 − , whereas human HSC are predominantly c- kit low , flt-3 + ( 11 ). (jimmunol.org)
  • as the donor-derived T cells exhibited a strong cytolytic activity, a poor proliferative response to mitogenic stimuli, and a tendency to home and expand specifically in the intestine upon transfer to secondary SCID recipients. (jimmunol.org)
  • Development of human CD4+FoxP3+ regulatory T cells in human stem cell factor-, granulocyte-macrophage colony-stimulating factor-, and interleukin-3-expressing NOD-SCID IL2Rγ(null) humanized mice. (semanticscholar.org)
  • Similarly, the ability of CD4 + T cells to differentiate into Foxp3 + natural regulatory T cells is preserved in rag1 and lig4 mutant mice, but their number is greatly reduced. (frontiersin.org)
  • We here describe the introduction of a mutation in RAG-1 into the germline of mice via gene targeting in embryonic stem cells. (nih.gov)
  • Because DNA-PK knockout and SCID mutant cell lines are viable, we reasoned that selective small molecule DNA-PK catalytic subunit inhibitors must sensitize cells to DSB-inducing treatments yet be nontoxic in the absence of DSBs ( 21 -23 ). (aacrjournals.org)
  • In the humanized mice, human leukocytes, including human CD4 + T cells, are successfully differentiated de novo and are stably and longitudinally maintained for more than 1 year ( 15 , 34 ). (asm.org)
  • Our humanized mice are capable of supporting persistent replication of CCR5-tropic HIV-1 for more than 7 months and mirror the characteristics of HIV-1 pathogenesis, such as the depletion of memory CD4 + T cells in the periphery and the preferential infection of effector memory T cells ( 34 ). (asm.org)
  • The discovery of nude mice, asplenic mice, and severe combined immunodeficiency ( scid ) mice has greatly accelerated studies on basic and applied immunology, because nude mice lack functional T cells by agenesis of the thymus, and asplenic mice show depressed Immunoglobulin levels [1]. (springer.com)
  • Kruisbeek AM, Mond JJ, Fowldes BJ, Carmen JA, Bridges S, Longo DL (1985) Absence of the Lyt-2-, L3T4+ lineage of T cells in mice treated neonatally with anti-I-A correlates with absence of intrathymic I-A-bearing antigenpresenting cell function. (springer.com)
  • Replication of the viruses with mutations of the gE promoter did not differ from control recombinants in melanoma cells or primary human tonsil T cells in vitro. (asm.org)
  • The importance of gE trafficking to the plasma membrane and the trans-Golgi network in infected cells is indicated by the lethal effect of deletion of the cytoplasmic C-terminal domain and mutation of the endocytosis motif located in this region ( 31 ). (asm.org)
  • Autologous, mutation-specific CD8 + T cells were identified in 23% (3/13) of evaluated cases. (aacrjournals.org)
  • Responding T cells showed exquisite specificity for mutant versus wild-type proteins and recognized lymphoma cells expressing the appropriate mutations. (aacrjournals.org)
  • Patients with follicular lymphoma harbor rare yet functionally competent CD8 + T cells specific for recurrent mutations. (aacrjournals.org)
  • 1996. Human delayed type hypersensitivity reaction in a SCID mouse engrafted with human T cells and autologous skin. (meduniwien.ac.at)
  • Next, 5 × 10(4) human umbilical cord blood CD34(+) cells were intravenously inoculated into irradiated adult or newborn of the immunodeficient mice. (jove.com)
  • We investigated the combined effects of vismodegib and ponatinib, a pan-ABL1 kinase inhibitor, in nonobese diabetic/severe-combined immunodeficiency (NOD/SCID) repopulating T315I BCR-ABL1-positive cells in vitro and in vivo . (aacrjournals.org)
  • Both human CD34-enriched cells (CD34 + ) and unfractionated mononuclear cells (MNCs) engrafted sublethally irradiated NSG-SGM3 mice after intrafemoral (IF) or IV injection. (bloodjournal.org)
  • Xenograft models of human acute leukemias that use ever-improving strains of immunocompromised mice have allowed for seminal investigations, including the identification and characterization of leukemia stem cells and preclinical testing of novel therapies. (bloodjournal.org)
  • We report a novel mutation of the IL-7Rα gene in a Korean SCID patient with a greatly diminished T-cell count but normal numbers of B-cells and natural killer (NK) cells. (springer.com)
  • The results of this study emphasize the importance of characterization of IL-7Rα mutations in SCID patients with diminished T-cell numbers but normal numbers of B-cells and NK cells. (springer.com)
  • Reduced switching in SCID B cells is associated with altered somatic mutation of recombined S regions. (southernbiotech.com)
  • Distinct phenotypes of plasma cells in spleen and bone marrow of autoimmune NOD.B10.H2b mice. (southernbiotech.com)
  • Gallagher MP, Shrestha A, Magee JM, Wesemann DR. Detection of true IgE-expressing mouse B lineage cells. (southernbiotech.com)
  • The Yaa mutation promoting murine lupus causes defective development of marginal zone B cells. (southernbiotech.com)
  • By providing a "kit" of preselected cells and mice, researchers save time and resources short-term spent on characterizing PBMCs putting them in control of study timing, a distinct advantage when dealing with a limited therapeutic window. (hemacare.com)
  • We report the emergence of polyclonal KRAS, NRAS, and BRAF mutations in CRC cells with acquired resistance to EGFR blockade. (sciencemag.org)
  • IL-7 plays an important role in the development of B and T cells in mouse and T cells in humans. (wikipathways.org)
  • After about two decades of experimentation in transplanting human tissues into mice, the latest round of rodents can successfully harbor human immune cells and can be infected with human viruses that mice are usually not susceptible to. (iavireport.org)
  • These SCID mice have a mutation in a DNA repair enzyme that leads to impairment in the genomic DNA rearrangements, which are responsible for creating the cornucopia of different B and T cells. (iavireport.org)
  • As a result, SCID mice can't make B or T cells, and therefore don't reject grafts of human tissue. (iavireport.org)
  • The resulting mice, known as SCID-hu mice, developed a thymus-like structure containing human T cells that could be infected with HIV ( Science 242, 1684, 1988). (iavireport.org)
  • Manz says the recipient mice only produced human immune cells for a limited time, maybe for a few weeks or months. (iavireport.org)
  • This is partly because CB17-SCID mice still maintain some innate immune responses such as natural killer (NK) cells and therefore eventually develop some mouse T and B cells, which causes them to reject some of the human cells. (iavireport.org)
  • Another drawback was that the HIV particles in infected SCID-hu mice remained mostly confined to the transplanted thymus tissue where the infection occurred, and as a result, biopsies were required to analyze the infected cells. (iavireport.org)
  • Then, a study published last year showed that the transplanted human cells engraft better in these mice than in SCID mice because of an additional impairment in their innate immune system. (iavireport.org)
  • Both cells and mice lacking DNA-PKcs show attenuated cytokine responses to both DNA and DNA viruses but not to RNA or RNA virus infection. (elifesciences.org)
  • When introduced into an immunodeficient mouse model (NOD scid gamma, or NSG mice), the edited human cells persisted for long periods. (mdedge.com)
  • At a media briefing where he discussed his research prior to his presentation of data in a symposium, Dr. Lundberg said that to date they have worked only with mouse models and with cells from healthy donors. (mdedge.com)
  • The contribution of B cells to the pathology of Omenn syndrome and leaky severe combined immunodeficiency (SCID) has not been previously investigated. (scialert.net)
  • In spite of a severe block at the pro-B cell stage and profound B cell lymphopenia, significant serum levels of immunoglobulin (Ig) G, IgM, IgA, and IgE and a high proportion of Ig-secreting cells were detected in mut/mut mice. (scialert.net)
  • We hypothesized that reduced expression of PU.1 in Sfpi1 BN/BN myeloid cells will result in the development of AML in transplanted mice due to reduced repression of E2F1, leading to deregulation of the cell cycle. (uwo.ca)
  • UCLA researchers led by Dr. Donald Kohn have created a method for modifying blood stem cells to reverse the genetic mutation that causes a life-threatening autoimmune syndrome called IPEX. (iran-daily.com)
  • Background Severe combined immunodeficiency (SCID) represents congenital disorders characterized by a deficiency of T cells caused by arrested development in the thymus. (eur.nl)
  • Methods We performed transplantation of SCID CD34+ bone marrow stem/progenitor cells into an optimized NSG xenograft mouse model, followed by detailed phenotypic and molecular characterization using flow cytometry, immunoglobulin and T-cell receptor spectratyping, and deep sequencing of immunoglobulin heavy chain (IGH) and T-cell receptor δ (TRD) loci. (eur.nl)
  • T-cell receptor rearrangements were functionally required at the CD4-CD8-CD7+CD5+ stage given the developmental block and extent of rearrangements in mice transplanted with Artemis-SCID cells. (eur.nl)
  • Conclusion Transplanting CD34+ stem cells from patients with SCID into a xenograft mouse model provides previously unattainable insight into human T-cell development and functionally identifies the arrest in thymic development caused by several SCID mutations. (eur.nl)
  • Patients with SCID have genetic defects that can affect T cells and at least one other type of immune cells. (bmbreports.org)
  • SCID is categorized into numerous types based on the cellular profile of immune cells. (bmbreports.org)
  • This review provides an overview of the current status of HSPC research with a focus on (i) assays used to detect and enumerate human and mouse stem and progenitor cells, (ii) phenotypic markers and methods used for their identification and isolation, and (iii) culture systems used to amplify stem and progenitor cells or to promote their differentiation in order to produce large numbers of mature blood cells for transfusion. (stemcell.com)
  • The hematopoietic potential of mouse HSCs is assayed by injection into mice in which hematopoiesis has been suppressed by irradiation or other methods, and measuring the repopulation of the recipient BM, blood, spleen and/or thymus with donorderived cells after a period of at least 4 months. (stemcell.com)
  • In one type of assay, lethally irradiated recipient mice are coinjected with congeneic donor-derived "test" cells along with syngeneic (host-type) "competitor" cells to provide shortterm radioprotection, ensure survival, and provide a selective pressure to identify stem cells with high competitive repopulating potential. (stemcell.com)
  • After sublethal irradiation these animals can be transplanted with donor "test" cells from wild-type mice without the need for co-transplanted radioprotective cells to promote survival. (stemcell.com)
  • Please note that the NSG carries the true null interleukin-2 receptor gamma chain mutation and should not be confused with other strains that express a truncated interleukin-2 receptor gamma chain as described in: "Modulation of hematopoiesis in mice with a truncated mutant of the interleukin-2 receptor gamma chain" Ohbo K et al. (jax.org)
  • During routine genetic screening of several immunoglobulin heavy chain congenic mouse strains in 1980, one of us (MB) was surprised to find that several mice in the C.B-17IIcr strain, which was being maintained in a specific-pathogen-free facility of the Fox Chase Cancer Center (Philadelphia, PA), did not express serum immunoglobulin of the appropriate allotype. (wisepress.com)
  • Comparison of Human Hematopoietic Reconstitution in Different Strains of Immunodeficient Mice. (semanticscholar.org)
  • Several other groups have reported attempts to establish xenograft models of CMML and JMML by using a number of different immunodeficient mouse strains with and without the addition of human myeloid supporting cytokines and with varying cell doses and sample sources. (bloodjournal.org)
  • In the SCID mice, Cyp4a10 and Cyp2b9 down-regulations were partially and fully blocked, respectively, whereas the regulation of other P450s and Fmo3 was similar in both strains. (aspetjournals.org)
  • E-protein glycosylated variants of New York (NY) strains of WN virus are more neuroinvasive in mice than the non-glycosylated variants. (ajtmh.org)
  • The most common method for identifying the progeny of transplanted HSCs is to use genetic differences between donor and recipient mouse strains. (stemcell.com)
  • Following an optimised ex vivo protocol, transplantation of potentially corrected scid haematopoietic progenitors into irradiated scid recipients has been carried out. (royalholloway.ac.uk)
  • Preliminary results of the ex vivo gene repair and transplantation experiment have indicated potential rescue of the T-cell compartment in a fraction of the scid transplant recipients. (royalholloway.ac.uk)
  • Reconstitution of Lymphocyte Subsets in Scid Mice by Transplantation of Fetal Primordia. (wisepress.com)
  • Immunobiology of Bone Marrow Transplantation: Studies Using Scid Mice. (wisepress.com)
  • Successful Liver Allografts in Mice by Combination with Allogeneic Bone Marrow Transplantation", Proc. (patentgenius.com)
  • Establishment of new SCID and nude mouse models of human B leukemia/lymphoma and effective therapy of the tumors with immunotoxin and monoclonal antibody: marked difference between the SCID and nude mouse models in the antitumor efficacy of monoclonal antibody. (semanticscholar.org)
  • These findings provide important insights into the biological effects of truncating PPM1D mutations, and uncover unique vulnerabilities associated with enhanced PPM1D activity which can be exploited for the therapeutic intervention of mutant pediatric brain tumors. (nature.com)
  • Mutant PI3K (PIK3CA) and loss of PTEN activity were sufficient, but not necessary, as predictors of sensitivity to the antitumor activity of the PI3K inhibitor PX-866 in the presence of wild-type Ras, whereas mutant oncogenic Ras was a dominant determinant of resistance, even in tumors with coexisting mutations in PIK3CA. (aacrjournals.org)
  • This murine autosomal recessive mutation should prove extremely useful in fundamental studies of radiation-induced DNA damage and repair. (pnas.org)
  • A congenic mouse that possesses both autosomal recessive mutations SCID (Prkdcscid) and beige (Lystbg) . (criver.com)
  • The autosomal recessive scid mutation results in defective immunoglobulin and T cell receptor gene rearrangement. (rupress.org)
  • Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID). (springer.com)
  • Mutations in JAK3 and γc have been shown to be associated with the autosomal recessive form of T-B + SCID. (wikipathways.org)
  • The xenograft model used is not informative for adenosine deaminase-SCID, whereas hypomorphic mutations lead to less severe arrests in development. (eur.nl)
  • Phenotype and Differentiation Stage of Scid Mouse Thymocytes. (wisepress.com)
  • These new selective inhibitors recapitulate the phenotype of DNA-PK defective cell lines including those from SCID mice. (aacrjournals.org)
  • 12,13 The BRGS solves both these problems because it does not carry the Prkdc mutation and, therefore, it does not possess the SCID phenotype observed in the NSG and NOG strain. (genoway.com)
  • The Prkdc knockout generates a SCID-like phenotype lacking proper T-cell and B-cell formation. (hemacare.com)
  • We established an experimental system to investigate the development, morphology, physiology and disorder of human organ and tissue which are maintained in the severe combined immunodeficient mice (SCID) for long period. (nii.ac.jp)
  • BALB/c mice that were physiologically immunosuppressed by repeated pregnancy for 2 years after C. burnetii infection ( 28 ) developed endocarditis with fibrin deposits, a generic sign of chronic lesions, but the incidence of endocarditis was low (2 out of 13 mice). (asm.org)
  • BALB/c mice that underwent cyclophosphamide treatment after C. burnetii infection developed endocarditis, but the cases were transient ( 1 ). (asm.org)
  • This does not occur if only single MHC class I components of the H-2 g7 haplotype are present, such as K d in BALB/c mice or D b in C57BL/6 mice, both of which develop only a low level of diabetes when B7.1 is expressed. (diabetesjournals.org)
  • BALB/c mouse splenocytes were stained with Mouse Anti-Mouse CD19-UNLB (SB Cat. (southernbiotech.com)
  • Paraffin embedded BALB/c mouse colon tissue section was stained with Goat Anti-Mouse IgA-FITC (SB Cat. (southernbiotech.com)
  • Vitamin A metabolism and mucosal immune function are distinct between BALB/c and C57BL/6 mice. (southernbiotech.com)
  • The daily dose of LGG supplied to the animals allocated to the LGG group was based on the previous results by Gill and Rutherfurd [7] evaluated in BALB/c mice and confirmed as effective at increasing the LGG counts in the caecum of scid mice in a pilot test carried out in-house prior to the commencement of the experiment. (scirp.org)
  • Transgenic Scid Mice With a Functionally Rearranged Immunoglobulin Heavy Chain Gene. (wisepress.com)
  • Other interests of mine include phenotypic analysis of transgenic and knockout mice, the use of genetically engineered mice to understand host pathogen interactions, and infectious diseases of frogs. (stanford.edu)
  • Fukuchi Y, Miyakawa Y, Kobayashi K, Kuramochi T, Shimamura K, Tamaoki N, Nomura T, Ueyama Y, Ito M. (1998) Cytokine dependent growth of human TF-1 leukemic cell line in human GM-CSF and IL-3 producing transgenic SCID mice. (taconic.com)
  • In their article, Yoshimi et al demonstrated the great capacity of human CMML and JMML samples to engraft immunocompromised mice with transgenic expression of human stem cell factor (SCF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin-3 in the NOD/SCID-Il2rγc null background (NSG-SGM3) (see figure). (bloodjournal.org)
  • 1996). A novel LacI transgenic mutation-detection system and its application to establish baseline mutation frequencies in the scid mouse. (ubc.ca)
  • Here we present a model of peripheral ALCL pathogenesis where the malignancy is initiated in early thymocytes, before T-cell receptor (TCR) β-rearrangement, which is bypassed in CD4/NPM-ALK transgenic mice following Notch1 expression. (cancerindex.org)
  • at the University of Guelph by an intercross of C.B-17 SCID/SCID to C57BL/6 bg/bg mice. (criver.com)
  • However, neither B6.H-2 g7 mice, in which H-2 g7 is expressed on the C57BL/6 genetic background, nor the nonobese resistant (NOR) mouse, in which H-2 g7 is expressed on a genetic background that is 88% similar to NOD mice, develop diabetes. (diabetesjournals.org)
  • Diabetes does not develop in congenic mice that express MHC H-2 g7 on a C57BL/6 background. (diabetesjournals.org)
  • Thus, in these mice, the presence of the predisposing MHC is not sufficient to overcome the resistance factors derived from the C57BL/KsJ mouse. (diabetesjournals.org)
  • For example, coxsackievirus and adenovirus receptor (CAR), the receptor for CVB, is expressed within human islets, but not mouse islets ( 4 , 9 - 11 ), and infection of C57BL/6 mice with CVB3 or CVB4 does not result in diabetes (unpublished data). (diabetesjournals.org)
  • Female C57BL/6 (B6) and SCID mice were infected orally with C. rodentium and assessed for bacterial colonization/translocation and P450 and flavin monooxygenase-3 (Fmo3) expression levels after 7 days. (aspetjournals.org)
  • Flow Cytometry Analysis: 0.25 μg of this antibody detected CD45 in one million C57BL/6 mouse splenocytes. (sigmaaldrich.com)
  • Thymomagenesis in the NOD-scid/scid mouse was associated with expression of an NOD mouse-unique endogenous ecotropic murine leukemia provirus locus (Emv-30, mapped to proximal region of chromosome 11) not expressed in the standard substrain NOD/Lt thymus. (pnas.org)
  • Then, this mouse falls into GVHD after several months of the rat thymus graft and dies. (nii.ac.jp)
  • The rat BMT scid mouse is the model which is extremely useful to study education effects to the T cell of the thymus. (nii.ac.jp)
  • When these tests revealed a complete absence of serum immunoglobulin, it became apparent that a mutation had probably occurred in the C.B-17IIcr line. (wisepress.com)
  • Further analysis revealed that a single breeding pair was respon- sible for all of the immunoglobulin negative mice and that the defect showed recessive inheritance. (wisepress.com)
  • The Effect of the scid Mutation on Mechanism and Control of Immunoglobulin Heavy and Light Chain Gene Rearrangement. (wisepress.com)
  • Limited Clonal Diversity of Serum Immunoglobulin in Leaky Scid Mice. (wisepress.com)
  • Pauciclonal B Cell Involvement in Production of Immunoglobulin in Scid Ig+ Mice. (wisepress.com)
  • A null mutation in basigin, an immunoglobulin superfamily mumber, indicates its importans roles in peri-implantation development and spermatogenesis'Dev. (nii.ac.jp)
  • The use of immunodeficient and genetically engineered mouse models that mimic the human disease has been crucial in validating the importance of these genetic pathways in prostate cancer. (hindawi.com)
  • Editing of the human genome to correct disease-causing mutations is a promising approach for the treatment of genetic disorders. (nature.com)
  • The genetic background, derived from inbred NOD mouse strain NOD/ShiLtJ, contributes reductions in innate immunity that include an absent hemolytic complement system, reduced dendritic cell function, and defective macrophage activity. (wikipedia.org)
  • Understanding and estimating the genetic hazards of exposure to chemical mutagens and anticancer drugs in humans requires the development of efficient systems for monitoring germ line mutation. (aacrjournals.org)
  • The results of this study show that the single-molecule PCR technique provides a new and efficient experimental system for monitoring the genetic effects of anticancer drugs, capable of detecting increases in mutation rates at clinically relevant doses of exposure. (aacrjournals.org)
  • The analysis of germ line mutation induction in mice currently provides the main source of experimental data for evaluating the genetic risk of exposure to chemical mutagens and anticancer drugs in humans ( 4 , 6 ). (aacrjournals.org)
  • However, for many years, substantial genetic and genomic differences between humans and mice have hampered the translatability of experimental findings in infectious and immune-related diseases, very often leading to clinical trial failures. (genoway.com)
  • In the C3H genetic background, the SCID mutation also blocked the down-regulation of Cyp3a11, Cyp3a25, Cyp2d22, and Cyp2c29. (aspetjournals.org)
  • 1 , 2 Mutation of NPM1 1 is one of the most common genetic alterations in adult acute myeloid leukemia (AML), occurring in about one-third of patients and accounting for 50-60% of all AML cases with normal karyotype. (haematologica.org)
  • MADRID - With some genetic sleight-of-hand, investigators hope to mimic a rare, naturally occurring mutation that protects some patients with beta-thalassemia or sickle-cell disease (SCD) from becoming symptomatic. (mdedge.com)
  • However, patient-derived non-small cell lung cancer (NSCLC) xenograft mouse models are relatively few in number and are limited in their degree of genetic characterization and validation. (biomedcentral.com)
  • Established xenograft models were characterized for common genetic aberrations, including detection of gene mutations within EGFR and KRAS, and genetic amplification of FGFR1 and cMET . (biomedcentral.com)
  • Genetic aberrations were detected in six of the models, including one model with an EGFR activating mutation (Exon19 Del), one model with KRAS mutation, one model with both KRAS mutation and cMET gene amplification, and three models with FGFR1 amplification. (biomedcentral.com)
  • Ten patient-derived NSCLC xenograft models were established containing a variety of genetic aberrations including EGFR activating mutation, KRAS mutation, and FGFR 1 and cMET amplification. (biomedcentral.com)
  • The scid Mutation Disrupts Gene Rearrangement at the Rejoining of Coding Strands. (wisepress.com)
  • Consistent with these observations, a deficiency in E2A proteins completely abrogates the developmental block observed in mice with defects in TCR rearrangement. (rupress.org)
  • SCID pig is considered to be the most efficient animal model for studying human SCID due to their similar genetics, anatomy, physiology, and lifespan. (bmbreports.org)
  • An ex vivo strategy to correct the classical scid mouse, a model of human DNA-dependent protein kinase catalytic subunit (DNA-PKcs, PRKDC) deficiency, is hereby presented. (royalholloway.ac.uk)
  • The nonobese diabetic scid mouse: model for spontaneous thymomagenesis associated with immunodeficiency. (pnas.org)
  • In the present study, we compared the clinical symptoms, the histopathology, and the survival rates of C. burnetii infection in SCID mice and immunocompetent mice to determine whether the SCID mouse could be used as an animal model for chronic Q fever. (asm.org)
  • The level of gene targeting achieved was sufficient to correct the prolonged clotting times in a mouse model of haemophilia B, and remained persistent after induced liver regeneration. (nature.com)
  • We generated a knockin mouse model harboring the RAG1-S723C hypomorphic mutation and examined the immune system in this fully in vivo setting. (bloodjournal.org)
  • The ICR scid spontaneous mutant model was developed by the Fox Chase Cancer Center by intercrossing ICR mice to C.B-17-SCID mice. (taconic.com)
  • In order to resolve the controversial role of viruses in human T1D, we developed a viral infection model in immunodeficient mice bearing human islet grafts. (diabetesjournals.org)
  • In this review our aim is not to suggest that the mouse is an invalid model system for human biology. (jimmunol.org)
  • Third, in a transfer model in which IEL suspensions are transferred to SCID recipients, we found that IEL preferentially populated intestinal as opposed to peripheral lymphoid tissue ( 25 ). (jimmunol.org)
  • A humanized mouse model of anaphylactic peanut allergy. (semanticscholar.org)
  • In this study, we use a human hematopoietic stem cell-transplanted humanized mouse (NOG-hCD34 mouse) model and demonstrate the predominant accumulation of G-to-A mutations in vif -proficient HIV-1 provirus displaying characteristics of APOBEC3-mediated mutagenesis. (asm.org)
  • By utilizing the humanized mice, we have established a novel animal model for HIV-1 infection ( 34 ). (asm.org)
  • reported the significance of HIV-1 mutation and its influence on HIV-1 expansion by using a humanized mouse model system ( 14 ). (asm.org)
  • In this study, by using the humanized mouse (NOG-hCD34 mouse) model, we show that G-to-A mutation of vif -proficient HIV-1 provirus exhibiting the characteristics of A3-mediated mutagenesis occurs in vivo . (asm.org)
  • 2012.Wnt1 Is Anti-Lymphangiogenic in a Melanoma Mouse Model.J Invest Dermatol. (meduniwien.ac.at)
  • Here we use a humanized mouse model and HIV-1 with mutations in Vif motifs that are responsible for specific APOBEC3 interactions, DRMR/AAAA (4A) or YRHHY/AAAAA (5A), and demonstrate that endogenous APOBEC3D/F and APOBEC3G exert strong anti-HIV-1 activity in vivo. (jove.com)
  • The SCID-hu Mouse: Murine Model for the Analysis of Human Hematolymphoid Differentiation and Function", Science 241:1632 (1988). (patentgenius.com)
  • As discussed in our previous commentary , mice are the experimental models of election in preclinical research, as they represent an affordable, rapidly reproducing and easily maintained mammalian model to study disease etiology and therapeutic assessment. (genoway.com)
  • For all these reasons, the BRGSF mouse model represents a valuable tool for vaccine development, efficacy and safety of chimeric antigen receptor (CAR) T cell therapy, and myeloid compartment development studies. (genoway.com)
  • The NCG mouse model is Charles River's most immunodeficient model to date. (hemacare.com)
  • We then adapted a previously designed mathematical model of hematopoietic tumorigenesis to analyze the age incidence of acute myeloid leukemia with mutated NPM1 and found that a one-mutation model can explain the incidence curve of this leukemia entity. (haematologica.org)
  • This model fits with the hypothesis that NPMc + acute myeloid leukemia arises from an NPM1 mutation with haploinsufficiency of the wild-type NPM1 allele. (haematologica.org)
  • Although the mouse model is one of the most fundamental in all of biomedical research, its use as a model system for HIV has been severely hampered by the fact that the virus is a uniquely human pathogen. (iavireport.org)
  • Still, many are optimistic that the humanized mouse model will someday soon provide valuable preclinical information on human immune responses to candidate vaccines. (iavireport.org)
  • For this, we use an in vivo model of severe combined immunodeficient ( scid ) mice supplemented daily with LGG over 8 weeks period. (scirp.org)
  • In this review, we focus on underlying mechanisms of human SCID, recent progress in the development of SCID animal models, and utilization of SCID pig model in biomedical sciences. (bmbreports.org)
  • Due to analogous features of pig to those of human, studies have found that immunodeficient pig is the most appropriate model for human SCID. (bmbreports.org)
  • These deletions did not affect infection of human skin xenografts in SCIDhu mice. (asm.org)
  • SCID mice with tumour xenografts with inducible MT1h expression had lower tumour volumes as well as fewer metastases and deaths than uninduced controls. (biomedsearch.com)
  • The NOG and NSG were largely used in PDX studies, as they sustain better engraftments of human tissues compared to NUDE and SCID mice. (genoway.com)
  • An unusually high incidence of spontaneous thymic lymphoma development was observed after transfer of this mutation from the C.B-17 congenic strain background onto the diabetes-susceptible nonobese diabetic (NOD) background. (pnas.org)
  • The nonobese diabetic (NOD) mouse, which develops spontaneous diabetes, expresses H-2 g7 comprising the MHC class I molecules K d and D b and the MHC class II molecule I-A g7 . (diabetesjournals.org)
  • To prepare the relatively human bone marrow environment in mice, we generated nonobese diabetic/severe combined immunodeficiency/interleukin-2 receptor gamma chain null (NOG) mice expressing human Jagged1 (hJ1) in an osteoblast-specific manner (hJ1-NOG mice) to examine whether Notch signaling induced by hJ1 mediates hHSC proliferation and/or maintenance in mice. (jove.com)
  • Immune depletion with cellular mobilization imparts immunoregulation and reverses autoimmune diabetes in nonobese diabetic mice. (southernbiotech.com)
  • Taken together, these results provide the evidence indicating that endogenous APOBEC3s are associated with G-to-A mutation of HIV-1 provirus in vivo , which can result in the abrogation of HIV-1 infection. (asm.org)
  • The general concept that during infection of mice the Borrelia burgdorferi surface protein composition differs profoundly from that of tick-borne or in vitro-cultivated spirochetes is well established. (asm.org)
  • OspA and OspB were not found in the tissues of SCID mice 17 days after infection. (asm.org)
  • Infection of the SCID-hu Mouse by HIV-1", Science 242:1684-1686 (1988). (patentgenius.com)
  • Pappo J, Torrey D, Castriotta L, Savinainen A, Kabok Z, Ibraghimov A. Helicobacter pylori infection in immunized mice lacking major histocompatibility complex class I and class II functions. (southernbiotech.com)
  • Testing for gene mutations linked to breast and ovarian cancer is rare among some Medicare patients who have the cancers and qualify for such tests, a new study found. (iran-daily.com)
  • Incorporation of the deletion or the point mutations disrupting both of the Sp1 binding sites into the VZV genome was not compatible with viral replication. (asm.org)
  • In this context, it is essential to identify AML-associated "driver" mutations, which have a causative role in leukemogenesis. (hindawi.com)
  • Evidences accumulated during the last years indicate that activating internal tandem duplication mutations in FLT3 (FLT3-ITD), detected in about 20% of AMLs, represents driver mutations and valid therapeutic targets in AMLs. (hindawi.com)
  • The scope of this review is to briefly outline recent evidences indicating that FLT3-ITD mutations are leukemic driver mutations and, therefore, represent important therapeutic targets. (hindawi.com)
  • T-cell responses were directed toward putative driver mutations in CREBBP and MEF2B. (aacrjournals.org)
  • Our results support the concept of using NGS to design individualized immunotherapies targeting common driver mutations in follicular lymphoma and other malignancies. (aacrjournals.org)
  • Nature of the scid Defect: A Defective VDJ Recombinase System. (wisepress.com)
  • Cell lines defective for DNA-PK function (knockout and SCID mutant cell lines) are sensitive to killing by DSB-inducing treatments ( 5 -8 ). (aacrjournals.org)
  • Although it has been suggested that defective interleukin 7 receptor (IL-7R) signaling is one of the principal causes of severe combined immunodeficiency disease (SCID) in mice and humans, little is known about the molecular and clinical characteristics of human IL-7Rα mutations. (springer.com)
  • In other assays, host mice are used that have defective endogenous hematopoiesis due to mutations in the c-Kit gene (e.g. (stemcell.com)
  • Human embryonic tissues also well developed and grew rapidly in SCID mice. (nii.ac.jp)
  • A variety of novel antigens, including antigens with molecular masses of 65 and 30 kDa, were found to be upregulated in mouse tissues. (asm.org)
  • The small numbers of HAB found in the tissues of infected mice have been regarded as insufficient for direct protein and antigenic analysis. (asm.org)
  • At that time, several groups transplanted human tissues into SCID mice. (iavireport.org)
  • Mut/mut mice produced high amounts of low-affinity self-reactive antibodies and showed significant lymphocytic infiltrates in peripheral tissues. (scialert.net)
  • NSCLC tissues from thirty-one patients were collected and implanted into immunodeficient mice. (biomedcentral.com)
  • AAV8-mediated delivery of F9 ZFNs to h F9 mut mouse liver results in cleavage of h F9 mut intron 1 in vivo . (nature.com)
  • Mice are the mainstay of in vivo immunological experimentation and in many respects they mirror human biology remarkably well. (jimmunol.org)
  • However, because there are so many parallels there has been a tendency to ignore differences and in many cases, perhaps, make the assumption that what is true in mice-in vivo veritas-is necessarily true in humans. (jimmunol.org)
  • Although subsequent investigations have revealed that lines of APOBEC3 family proteins have the capacity to mutate HIV-1 DNA, it remains unclear whether these endogenous APOBEC3s, including APOBEC3G, contribute to mutations of vif -proficient HIV-1 provirus in vivo and, if so, what is the significance of these mutations. (asm.org)
  • ZFN- and template-mediated gene repair of the scid mutation was demonstrated via the incorporation of a selection cassette and/or a diagnostic restriction site from the donor template into the targeted locus. (royalholloway.ac.uk)
  • The heterozygous, truncating mutations were introduced into exon 6 of the PPM1D locus, at C-terminal locations similar to those found in DIPGs (Fig. 1a ). (nature.com)
  • Here we show that ZFNs are able to induce DSBs efficiently when delivered directly to mouse liver and that, when co-delivered with an appropriately designed gene-targeting vector, they can stimulate gene replacement through both homology-directed and homology-independent targeted gene insertion at the ZFN-specified locus. (nature.com)
  • The suitability of a single-molecule PCR-based approach for monitoring mutation induction at the mouse expanded simple tandem repeat (ESTR) locus Ms6-hm by chemical mutagens and anticancer drugs has been validated. (aacrjournals.org)
  • The majority of the mouse data have been generated using either the specific locus method (Russell 7-locus test) or the dominant lethal test ( 4 , 6 ). (aacrjournals.org)
  • This suggests that the gamma-ray sensitivity of the scid mouse fibroblasts could be the result of reduced repair of DNA double-strand breaks. (pnas.org)
  • The sensitivity of scid fibroblasts established from C.B17-scid/scid fetuses to the DNA-damaging agents bleomycin, neocarzinostatin, mechlorethamine, mitomycin C, methyl methanesulfonate, and ultraviolet light, all of which induce different types of DNA damage, was examined. (nih.gov)
  • Most importantly, these tests lack the sensitivity to detect mutation induction in the germ line of mice exposed to low and often intermediate concentrations of chemical mutagens. (aacrjournals.org)
  • Unstable ESTR loci consist of homogenous arrays of short repeats (4-6 bp) and show very high spontaneous mutation rates in the mouse germ line, observed as size changes in the alleles of these loci ( 10 - 12 ). (aacrjournals.org)
  • They discovered that the four mice, littermates, were sired by a male with a spontaneous mutation in an unknown gene that was apparently essential for the development of a normal immune system. (calvin.edu)
  • Specific ZFN activity in mouse scid fibroblasts and haematopoietic progenitors was demonstrated by Cel-I assay (which detects modifications introduced at the target site upon repair by non-homologous end-joining) and by deep sequencing. (royalholloway.ac.uk)
  • In scid fibroblasts, gene repair led to DNA-PKcs activity rescue and increased resistance to DNA damage. (royalholloway.ac.uk)
  • These mice are resistant to lymphoma development even after sublethal irradiation treatment. (jax.org)
  • Frequent p53 Mutations at Dipyrimidine Sites in Patients with Pyothoraxassosiated Lymphoma. (nii.ac.jp)
  • A number of mouse models genetically engineered to harbor mutations common to CMML and JMML have provided important mechanistic insights into disease pathogenesis. (bloodjournal.org)
  • Immunodeficient mice engrafted with human HSCs support multidisciplinary translational experimentation, including the study of human hematopoiesis. (semanticscholar.org)
  • Long-Term Human Hematopoiesis in the SCID-hu Mouse", J. Exp. (patentgenius.com)
  • The Prkdc scid mutation was identified by Mel Bosma of the Fox Chase Cancer Center in a C.B-17 congenic mouse population. (taconic.com)
  • The immunodeficient NSG mice enable research in human immune function, infectious disease, diabetes, oncology, and stem cell biology. (jax.org)
  • Growth and metastasis of fresh human melanoma tissue in mice with severe combined immunodeficiency. (semanticscholar.org)
  • To develop PPM1D mutant models for subsequent biological investigations, we used CRISPR/Cas9 genomic editing to create isogenic immortalized human astrocytes harboring endogenous PPM1D truncation mutations (PPM1D trncs. ). (nature.com)
  • Mouse anti-Interleukin-2 Soluble Receptor γ antibody reacts specifically with human IL-2 soluble receptor γ. (sigmaaldrich.com)
  • Human and mouse hematopoieisis. (intechopen.com)
  • However, the expression of the B7.1 molecule on the pancreas will allow development of spontaneous diabetes in B6 mice if the MHC class II molecule (in this case, I-A b ) is replaced by human MHC class II molecules that predispose to autoimmune diabetes ( 11 , 12 ). (diabetesjournals.org)
  • Human islet grafts from infected mice contained viral RNA, expressed viral protein, and had reduced insulin levels compared with grafts from uninfected mice. (diabetesjournals.org)
  • Hyperglycemic mice were engrafted with human islets to restore normoglycemia and then were infected with CVB4. (diabetesjournals.org)
  • Labeled iodine was incorporated into human thyroid gland maintained in the SCID mice more actively by the injection of human TSH to the mice. (nii.ac.jp)
  • Human skin transplanted to the SCID mice were exposed to ultraviolet light B (UVB) for long period. (nii.ac.jp)
  • Consecutive maintenance of human solitary and hereditary colorectal polyps in SCID mice. (nii.ac.jp)
  • Induction of cancer,actinic keratosis and specific p53 mutations by ultraviolet light B in human skin manitained in SCID mice. (nii.ac.jp)
  • Mice are the experimental tool of choice for the majority of immunologists and the study of their immune responses has yielded tremendous insight into the workings of the human immune system. (jimmunol.org)
  • Such differences should be taken into account when using mice as preclinical models of human disease. (jimmunol.org)
  • By making such assumptions we run the risk of overlooking aspects of human immunology that do not occur, or cannot be modeled, in mice. (jimmunol.org)
  • Included in this subset will be differences that may preclude a successful preclinical trial in mice becoming a successful clinical trial in human. (jimmunol.org)
  • As therapies for human diseases become ever more sophisticated and specifically targeted, it becomes increasingly important to understand the potential limitations of extrapolating data from mice to humans. (jimmunol.org)
  • By focusing on some known differences between mouse and human immunology we hope to spur interest in this area and encourage others to note differences where they occur. (jimmunol.org)
  • Additional studies are focusing on the circuit-level and molecular mechanisms that regulate incorporation of transplanted mouse or human GABAergic interneuron progenitors into host brains. (intechopen.com)
  • However, no difference was found in the human cell populations differentiated from HSCs between NR2G and NOG mice. (jove.com)
  • Transfer of a functional human immune system to mice with severe combined immunodeficiency", Nature 225:256-259 (1988). (patentgenius.com)
  • Giovanella et al, "Heterotransplantation of Human Cancers into Nude Mice", Cancer 42:2269-2281 (1978). (patentgenius.com)
  • RAG mutations in human B cell-negative SCID. (springer.com)
  • Utilizing PBMC humanized mice that most closely mimic the human immune system has become an industry standard particularly for immuno-oncology and cell therapy. (hemacare.com)
  • Immunodeficient mouse models that support multilineage human immune cell reconstitution embody a more biologically relevant simulation of human immune response. (hemacare.com)
  • New mice, which are being developed by researchers, may not don capes or fight villains but they do possess other super powers, brought on by the fact that they have human immune systems. (iavireport.org)
  • The first humanized mice were generated around 20 years ago by transplanting human tissue into strain CB17 severe combined immunodeficiency (SCID) mice. (iavireport.org)
  • Another group led by Donald Mosier, then at the Medical Biology Institute and now a professor at the Scripps Research Institute in California, injected human peripheral blood leukocytes (PBL) into the peritoneal cavity of SCID mice, generating Hu-PBL-SCID mice ( Nature 335, 256, 1988). (iavireport.org)
  • NOD mice develop autoimmune diabetes, but NOD-SCID mice don't because they lack the ability to generate immune responses and, as it turned out, they were also much more accommodating for transplanted human tissue. (iavireport.org)
  • Objective We sought to identify the stages of arrest in human T-cell development caused by various major types of SCID. (eur.nl)
  • Pleiotropic Effects of the scid Mutation: Effects on Lymphoid Differentiation and on Repair of Radiation Damage. (wisepress.com)
  • One difference worth noting is that whereas mice have significant bronchus-associated lymphoid tissue, this is largely absent in healthy humans ( 9 ), possibly reflecting a higher breathable Ag load for animals living so much closer to the ground. (jimmunol.org)
  • Mutation of Jak3 in a patient with SCID: essential role of Jak3 in lymphoid development. (springer.com)
  • Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients. (nature.com)
  • Homozygosity for the severe combined immunodeficiency (scid) mutation results in a block in T- and B-lymphocyte development. (pnas.org)
  • Detection of a Potential B Lymphocyte Progenitor Population Present at Normal Levels in Scid Mice by Three Color Flow Cytometry With B220 and S7. (wisepress.com)
  • Use of the Scid Mouse Tranplantation System in Studies of Lymphocyte Differentiation. (wisepress.com)
  • The scid mouse presented a new big question for the Bosmas: Just how did the scid mutation impair lymphocyte development? (calvin.edu)
  • These findings indicate that the scid mutation in mice causes defects in repairing both double-strand DNA breaks and DNA cross-links. (nih.gov)
  • These data indicate that the stochastic generation of an autoreactive B cell repertoire, which is associated with defects in central and peripheral checkpoints of B cell tolerance, is an important, previously unrecognized, aspect of immunodeficiencies associated with hypomorphic RAG mutations. (scialert.net)
  • Suppression of spontaneous melanoma metastasis in scid mice with an antibody to the epidermal growth factor receptor. (semanticscholar.org)
  • Mutations in CD45 have been associated with Multiple Sclerosis (MS) and severe combined immunodeficiency (SCID), a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. (sigmaaldrich.com)
  • The SCID mouse is highly susceptible to C. burnetii , and the immunodeficiency of the host enhances the severity of Q fever. (asm.org)
  • The Prkdcscid mutationa, commonly known as "scid" or "severe combined immunodeficiency", essentially eliminates adaptive immunity. (wikipedia.org)
  • Bosma GC, Custer RP, Bosma MJ (1983) A severe combined immunodeficiency mutation in the mouse. (springer.com)
  • studied potential approaches to it in mouse models of severe combined immunodeficiency. (sciencemag.org)
  • A Severe Combined Immunodeficiency Mutation in the Mouse", Nature 301:527 (1983). (patentgenius.com)
  • Interleukin-2 receptor γ chain mutation results in X-linked severe combined immunodeficiency in humans. (springer.com)
  • Mutations in the tyrosine phosphatase CD45 gene in a child with severe combined immunodeficiency disease. (springer.com)
  • DNA-PK has well-established functions in the DNA repair and V(D)J recombination, hence loss of DNA-PK leads to severe combined immunodeficiency (SCID). (elifesciences.org)
  • Autoantibodies and elevated BAFF levels were also identified in patients with Omenn syndrome and leaky SCID as a result of hypomorphic RAG mutations. (scialert.net)
  • While the ability of mTECs to express autoimmune regulator (Aire) is preserved in mutant mice, the frequency of mature mTECs expressing Aire and tissue-specific antigens is severely reduced. (frontiersin.org)
  • The immune system of the RAG-1 mutant mice can be described as that of nonleaky scid mice. (nih.gov)
  • Systemic autoimmunity in BAFF-R-mutant A/WySnJ strain mice. (southernbiotech.com)
  • The heart lesions of the SCID mice were similar to those in humans with chronic Q fever endocarditis: they had focal calcification and expanded macrophages containing C. burnetii . (asm.org)
  • Despite this conservation there exist significant differences between mice and humans in immune system development, activation, and response to challenge, in both the innate and adaptive arms. (jimmunol.org)
  • The literature is littered with examples of therapies that work well in mice but fail to provide similar efficacy in humans ( 2 , 3 , 4 , 5 , 6 , 7 ). (jimmunol.org)
  • The overall structure of the immune system in mice and humans is quite similar. (jimmunol.org)
  • Mutation of the gene encoding PU.1, SPI1 in humans and Sfpi1 in mice, is associated with AML. (uwo.ca)
  • A naturally occurring SCID in humans was first described in the 1960s. (bmbreports.org)
  • How to establish acute myeloid leukemia xenograft models using immunodeficient mice. (semanticscholar.org)
  • FLT3 internal tandem duplication, cooperate with NPM1 mutations in acute myeloid leukemia development. (haematologica.org)
  • The SCID mice examined in this study had severe chronic lesions in their primary organs: the heart, lung, spleen, liver, and kidney. (asm.org)
  • On the other hand, when transplanting the thymic lobes of the 15th of embryonic rats under the kidney capsule of scid mouse, the lobes grow. (nii.ac.jp)
  • Blood tests of these particular four mice showed they lacked an antibody marker specific to the strain under study. (calvin.edu)
  • Recently, it has been shown that ospC synthesis wanes in apparent response to the synthesis of OspC antibody by infected mice ( 31 ). (asm.org)
  • Anti-CD45 (mouse) Antibody, PE, clone 30-F11 is a highly specific rat monoclonal antibody, that targets CD45 & has been tested in Flow Cytometry, IHC, Activity Assay, IP & western blotting. (sigmaaldrich.com)
  • Furthermore, the screening of FLT3-ITD mutations has also considerably helped to improve the identification of more accurate prognostic criteria and of the therapeutic selection of patients. (hindawi.com)
  • in fact, internal tandem duplications (ITDs) within the juxtamembrane domain of FLT3 have been reported in about 25% of patients, making it one of the most single frequent mutations in adult AMLs [ 1 ]. (hindawi.com)
  • In addition, several recent molecular studies have clearly identified subsets of AML patients, whose prognosis is considerably worsened by FLT3-ITD mutations and could considerably benefit from an efficacious FLT3 pharmacological targeting. (hindawi.com)
  • The gene therapy, which was tested in mice, is similar to the technique Kohn has used to cure patients with another immune disease, severe combined immune deficiency, or SCID, also known as bubble baby disease. (iran-daily.com)
  • Ten passable patient-derived NSCLC xenograft models were established by implantation of NSCLC specimens of thirty-one patients into immunodeficient mice. (biomedcentral.com)