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.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
Techniques to alter a gene sequence that result in an inactivated gene, or one in which the expression can be inactivated at a chosen time during development to study the loss of function of a gene.
A family of the order Rodentia containing 250 genera including the two genera Mus (MICE) and Rattus (RATS), from which the laboratory inbred strains are developed. The fifteen subfamilies are SIGMODONTINAE (New World mice and rats), CRICETINAE, Spalacinae, Myospalacinae, Lophiomyinae, ARVICOLINAE, Platacanthomyinae, Nesomyinae, Otomyinae, Rhizomyinae, GERBILLINAE, Dendromurinae, Cricetomyinae, MURINAE (Old World mice and rats), and Hydromyinae.
Critical and exhaustive investigation or experimentation, having for its aim the discovery of new facts and their correct interpretation, the revision of accepted conclusions, theories, or laws in the light of newly discovered facts, or the practical application of such new or revised conclusions, theories, or laws. (Webster, 3d ed)
Diseases of rodents of the order RODENTIA. This term includes diseases of Sciuridae (squirrels), Geomyidae (gophers), Heteromyidae (pouched mice), Castoridae (beavers), Cricetidae (rats and mice), Muridae (Old World rats and mice), Erethizontidae (porcupines), and Caviidae (guinea pigs).
Congenital defect in the upper lip where the maxillary prominence fails to merge with the merged medial nasal prominences. It is thought to be caused by faulty migration of the mesoderm in the head region.
Disorders in which there is a delay in development based on that expected for a given age level or stage of development. These impairments or disabilities originate before age 18, may be expected to continue indefinitely, and constitute a substantial impairment. Biological and nonbiological factors are involved in these disorders. (From American Psychiatric Glossary, 6th ed)
The prevailing temper or spirit of an individual or group in relation to the tasks or functions which are expected.
Congenital fissure of the soft and/or hard palate, due to faulty fusion.
A genus of GRAM-POSITIVE ENDOSPORE-FORMING RODS, in the family Alicyclobacillaceae, containing a unique lipid in their membranes.
The interaction of persons or groups of persons representing various nations in the pursuit of a common goal or interest.
The genetic complement of an organism, including all of its GENES, as represented in its DNA, or in some cases, its RNA.
The co-inheritance of two or more non-allelic GENES due to their being located more or less closely on the same CHROMOSOME.
A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event.
Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc.
Symptom of overactive detrusor muscle of the URINARY BLADDER that contracts with abnormally high frequency and urgency. Overactive bladder is characterized by the frequent feeling of needing to urinate during the day, during the night, or both. URINARY INCONTINENCE may or may not be present.
Failure of voluntary control of the anal sphincters, with involuntary passage of feces and flatus.
Involuntary discharge of URINE as a result of physical activities that increase abdominal pressure on the URINARY BLADDER without detrusor contraction or overdistended bladder. The subtypes are classified by the degree of leakage, descent and opening of the bladder neck and URETHRA without bladder contraction, and sphincter deficiency.
A musculomembranous sac along the URINARY TRACT. URINE flows from the KIDNEYS into the bladder via the ureters (URETER), and is held there until URINATION.
Involuntary discharge of URINE that is associated with an abrupt and strong desire to void. It is usually related to the involuntary contractions of the detrusor muscle of the bladder (detrusor hyperreflexia or detrusor instability).
A sympathomimetic that acts mainly by causing release of NOREPINEPHRINE but also has direct agonist activity at some adrenergic receptors. It is most commonly used as a nasal vasoconstrictor and an appetite depressant.
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).
A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).
A subclass of DIABETES MELLITUS that is not INSULIN-responsive or dependent (NIDDM). It is characterized initially by INSULIN RESISTANCE and HYPERINSULINEMIA; and eventually by GLUCOSE INTOLERANCE; HYPERGLYCEMIA; and overt diabetes. Type II diabetes mellitus is no longer considered a disease exclusively found in adults. Patients seldom develop KETOSIS but often exhibit OBESITY.
Irregular microscopic structures consisting of cords of endocrine cells that are scattered throughout the PANCREAS among the exocrine acini. Each islet is surrounded by connective tissue fibers and penetrated by a network of capillaries. There are four major cell types. The most abundant beta cells (50-80%) secrete INSULIN. Alpha cells (5-20%) secrete GLUCAGON. PP cells (10-35%) secrete PANCREATIC POLYPEPTIDE. Delta cells (~5%) secrete SOMATOSTATIN.
Hepatocyte nuclear factor 1-alpha is a transcription factor found in the LIVER; PANCREAS; and KIDNEY that regulates HOMEOSTASIS of GLUCOSE.
A hepatocyte nuclear factor that is closely related to HEPATOCYTE NUCLEAR FACTOR 1-ALPHA but is only weakly expressed in the LIVER. Mutations in hepatocyte nuclear factor 1-beta are associated with renal CYSTS and MATURITY-ONSET DIABETES MELLITUS type 5.
A defect of leukocyte function in which phagocytic cells ingest but fail to digest bacteria, resulting in recurring bacterial infections with granuloma formation. When chronic granulomatous disease is caused by mutations in the CYBB gene, the condition is inherited in an X-linked recessive pattern. When chronic granulomatous disease is caused by CYBA, NCF1, NCF2, or NCF4 gene mutations, the condition is inherited in an autosomal recessive pattern.
PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.
A CALCIUM-dependent, constitutively-expressed form of nitric oxide synthase found primarily in ENDOTHELIAL CELLS.
Method in which repeated blood pressure readings are made while the patient undergoes normal daily activities. It allows quantitative analysis of the high blood pressure load over time, can help distinguish between types of HYPERTENSION, and can assess the effectiveness of antihypertensive therapy.
Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.
The number of times the HEART VENTRICLES contract per unit of time, usually per minute.
Techniques for measuring blood pressure.
An NADPH-dependent enzyme that catalyzes the conversion of L-ARGININE and OXYGEN to produce CITRULLINE and NITRIC OXIDE.
A compound formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids.
The ability of the kidney to excrete in the urine high concentrations of solutes from the blood plasma.
Membrane proteins whose primary function is to facilitate the transport of molecules across a biological membrane. Included in this broad category are proteins involved in active transport (BIOLOGICAL TRANSPORT, ACTIVE), facilitated transport and ION CHANNELS.
Urination of a large volume of urine with an increase in urinary frequency, commonly seen in diabetes (DIABETES MELLITUS; DIABETES INSIPIDUS).
Impaired conduction of cardiac impulse that can occur anywhere along the conduction pathway, such as between the SINOATRIAL NODE and the right atrium (SA block) or between atria and ventricles (AV block). Heart blocks can be classified by the duration, frequency, or completeness of conduction block. Reversibility depends on the degree of structural or functional defects.
A group of antigens consisting principally of Jk(a) and Jk(b), determined by allelic genes. Amorphs are encountered. Antibodies of these substances are usually weak and quite labile, stimulated by erythrocytes.

Molecular chaperones: small heat shock proteins in the limelight. (1/61166)

Small heat shock proteins have been the Cinderellas of the molecular chaperone world, but now the crystal structure of a small heat shock protein has been solved and mutation of two human homologues implicated in genetic disease. Intermediate filaments appear to be one of the key targets of their chaperone activity.  (+info)

Alzheimer's disease: clues from flies and worms. (2/61166)

Presenilin mutations give rise to familial Alzheimer's disease and result in elevated production of amyloid beta peptide. Recent evidence that presenilins act in developmental signalling pathways may be the key to understanding how senile plaques, neurofibrillary tangles and apoptosis are all biochemically linked.  (+info)

JNK2 is required for efficient T-cell activation and apoptosis but not for normal lymphocyte development. (3/61166)

BACKGROUND: The Jun N-terminal kinase (JNK) signaling pathway has been implicated in cell proliferation and apoptosis, but its function seems to depend on the cell type and inducing signal. In T cells, JNK has been implicated in both antigen-induced activation and apoptosis. RESULTS: We generated mice lacking the JNK2 isozymes. The mutant mice were healthy and fertile but defective in peripheral T-cell activation induced by antibody to the CD3 component of the T-cell receptor (TCR) complex - proliferation and production of interleukin-2 (IL-2), IL-4 and interferon-gamma (IFN-gamma) were reduced. The proliferation defect was restored by exogenous IL-2. B-cell activation was normal in the absence of JNK2. Activation-induced peripheral T-cell apoptosis was comparable between mutant and wild-type mice, but immature (CD4(+) CD8(+)) thymocytes lacking JNK2 were resistant to apoptosis induced by administration of anti-CD3 antibody in vivo. The lack of JNK2 also resulted in partial resistance of thymocytes to anti-CD3 antibody in vitro, but had little or no effect on apoptosis induced by anti-Fas antibody, dexamethasone or ultraviolet-C (UVC) radiation. CONCLUSIONS: JNK2 is essential for efficient activation of peripheral T cells but not B cells. Peripheral T-cell activation is probably required indirectly for induction of thymocyte apoptosis resulting from administration of anti-CD3 antibody in vivo. JNK2 functions in a cell-type-specific and stimulus-dependent manner, being required for apoptosis of immature thymocytes induced by anti-CD3 antibody but not for apoptosis induced by anti-Fas antibody, UVC or dexamethasone. JNK2 is not required for activation-induced cell death of mature T cells.  (+info)

Reduced water permeability and altered ultrastructure in thin descending limb of Henle in aquaporin-1 null mice. (4/61166)

It has been controversial whether high water permeability in the thin descending limb of Henle (TDLH) is required for formation of a concentrated urine by the kidney. Freeze-fracture electron microscopy (FFEM) of rat TDLH has shown an exceptionally high density of intramembrane particles (IMPs), which were proposed to consist of tetramers of aquaporin-1 (AQP1) water channels. In this study, transepithelial osmotic water permeability (Pf) was measured in isolated perfused segments (0.5-1 mm) of TDLH in wild-type (+/+), AQP1 heterozygous (+/-), and AQP1 null (-/-) mice. Pf was measured at 37 degrees C using a 100 mM bath-to-lumen osmotic gradient of raffinose, and fluorescein isothiocyanate (FITC)-dextran as the luminal volume marker. Pf was (in cm/s): 0.26 +/- 0.02 ([+/+]; SE, n = 9 tubules), 0.21 +/- 0.01 ([+/-]; n = 12), and 0.031 +/- 0.007 ([-/-]; n = 6) (P < 0.02, [+/+] vs. [+/-]; P < 0.0001, [+/+] vs. [-/-]). FFEM of kidney medulla showed remarkably fewer IMPs in TDLH from (-/-) vs. (+/+) and (+/-) mice. IMP densities were (in microm-2, SD, 5-12 micrographs): 5,880 +/- 238 (+/+); 5,780 +/- 450 (+/-); and 877 +/- 420 (-/-). IMP size distribution analysis revealed mean IMP diameters of 8.4 nm ([+/+] and [+/-]) and 5.2 nm ([-/-]). These results demonstrate that AQP1 is the principal water channel in TDLH and support the view that osmotic equilibration along TDLH by water transport plays a key role in the renal countercurrent concentrating mechanism. The similar Pf and AQP1 expression in TDLH of (+/+) and (+/-) mice was an unexpected finding that probably accounts for the unimpaired urinary concentrating ability in (+/-) mice.  (+info)

A genetic model of substrate deprivation therapy for a glycosphingolipid storage disorder. (5/61166)

Inherited defects in the degradation of glycosphingolipids (GSLs) cause a group of severe diseases known as GSL storage disorders. There are currently no effective treatments for the majority of these disorders. We have explored a new treatment paradigm, substrate deprivation therapy, by constructing a genetic model in mice. Sandhoff's disease mice, which abnormally accumulate GSLs, were bred with mice that were blocked in their synthesis of GSLs. The mice with simultaneous defects in GSL synthesis and degradation no longer accumulated GSLs, had improved neurologic function, and had a much longer life span. However, these mice eventually developed a late-onset neurologic disease because of accumulation of another class of substrate, oligosaccharides. The results support the validity of the substrate deprivation therapy and also highlight some limitations.  (+info)

Interleukin-8 receptor modulates IgE production and B-cell expansion and trafficking in allergen-induced pulmonary inflammation. (6/61166)

We examined the role of the interleukin-8 (IL-8) receptor in a murine model of allergen-induced pulmonary inflammation using mice with a targeted deletion of the murine IL-8 receptor homologue (IL-8r-/-). Wild-type (Wt) and IL-8r-/- mice were systemically immunized to ovalbumin (OVA) and were exposed with either single or multiple challenge of aerosolized phosphate-buffered saline (OVA/PBS) or OVA (OVA/OVA). Analysis of cells recovered from bronchoalveolar lavage (BAL) revealed a diminished recruitment of neutrophils to the airway lumen after single challenge in IL-8r-/- mice compared with Wt mice, whereas multiply challenged IL-8r-/- mice had increased B cells and fewer neutrophils compared with Wt mice. Both Wt and IL-8r-/- OVA/OVA mice recruited similar numbers of eosinophils to the BAL fluid and exhibited comparable degrees of pulmonary inflammation histologically. Both total and OVA-specific IgE levels were greater in multiply challenged IL-8r-/- OVA/OVA mice than in Wt mice. Both the IL-8r-/- OVA/OVA and OVA/PBS mice were significantly less responsive to methacholine than their respective Wt groups, but both Wt and IL-8r mice showed similar degrees of enhancement after multiple allergen challenge. The data demonstrate that the IL-8r modulates IgE production, airway responsiveness, and the composition of the cells (B cells and neutrophils) recruited to the airway lumen in response to antigen.  (+info)

Lung fluid transport in aquaporin-1 and aquaporin-4 knockout mice. (7/61166)

The mammalian lung expresses water channel aquaporin-1 (AQP1) in microvascular endothelia and aquaporin-4 (AQP4) in airway epithelia. To test whether these water channels facilitate fluid movement between airspace, interstitial, and capillary compartments, we measured passive and active fluid transport in AQP1 and AQP4 knockout mice. Airspace-capillary osmotic water permeability (Pf) was measured in isolated perfused lungs by a pleural surface fluorescence method. Pf was remarkably reduced in AQP1 (-/-) mice (measured in cm/s x 0.001, SE, n = 5-10: 17 +/- 2 [+/+]; 6.6 +/- 0.6 AQP1 [+/-]; 1.7 +/- 0.3 AQP1 [-/-]; 12 +/- 1 AQP4 [-/-]). Microvascular endothelial water permeability, measured by a related pleural surface fluorescence method in which the airspace was filled with inert perfluorocarbon, was reduced more than 10-fold in AQP1 (-/-) vs. (+/+) mice. Hydrostatically induced lung interstitial and alveolar edema was measured by a gravimetric method and by direct measurement of extravascular lung water. Both approaches indicated a more than twofold reduction in lung water accumulation in AQP1 (-/-) vs. (+/+) mice in response to a 5- to 10-cm H2O increase in pulmonary artery pressure for five minutes. Active, near-isosmolar alveolar fluid absorption (Jv) was measured in in situ perfused lungs using 125I-albumin as an airspace fluid volume marker. Jv (measured in percent fluid uptake at 30 min, n = 5) in (+/+) mice was 6.0 +/- 0.6 (37 degrees C), increased to 16 +/- 1 by beta-agonists, and inhibited to less than 2.0 by amiloride, ouabain, or cooling to 23 degrees C. Jv (with isoproterenol) was not affected by aquaporin deletion (18.9 +/- 2.2 [+/+]; 16.4 +/- 1.5 AQP1 [-/-]; 16.3 +/- 1.7 AQP4 [-/-]). These results indicate that osmotically driven water transport across microvessels in adult lung occurs by a transcellular route through AQP1 water channels and that the microvascular endothelium is a significant barrier for airspace-capillary osmotic water transport. AQP1 facilitates hydrostatically driven lung edema but is not required for active near-isosmolar absorption of alveolar fluid.  (+info)

GM-CSF-deficient mice are susceptible to pulmonary group B streptococcal infection. (8/61166)

Granulocyte-macrophage colony-stimulating factor (GM-CSF) gene-targeted mice (GM-/-) cleared group B streptococcus (GBS) from the lungs more slowly than wild-type mice. Expression of GM-CSF in the respiratory epithelium of GM-/- mice improved bacterial clearance to levels greater than that in wild-type GM+/+ mice. Acute aerosolization of GM-CSF to GM+/+ mice significantly enhanced clearance of GBS at 24 hours. GBS infection was associated with increased neutrophilic infiltration in lungs of GM-/- mice, while macrophage infiltrates predominated in wild-type mice, suggesting an abnormality in macrophage clearance of bacteria in the absence of GM-CSF. While phagocytosis of GBS was unaltered, production of superoxide radicals and hydrogen peroxide was markedly deficient in macrophages from GM-/- mice. Lipid peroxidation, assessed by measuring the isoprostane 8-iso-PGF2alpha, was decreased in the lungs of GM-/- mice. GM-CSF plays an important role in GBS clearance in vivo, mediated in part by its role in enhancing superoxide and hydrogen peroxide production and bacterial killing by alveolar macrophages.  (+info)

Many neurotransmitters, hormones and sensory stimuli elicit their cellular responses through the targeted activation of receptors coupled to Gq family heterotrimeric G proteins. Nevertheless, we still understand little about the consequences of loss of this signaling activity on brain function. We therefore examined the effects of genetic inactivation of Gnaq on responsiveness in a battery of behavioral tests in order to assess the contribution of Gaq signaling capacity in the brain circuits mediating expression of affective behaviors (anxiety and behavioral despair), spatial working memory and locomotor output (coordination, strength, spontaneous activity and drug-induced responses). First, we replicated and extended findings showing clear motor deficits in Gaq knockout mice as assessed on an accelerating rotarod and the inverted screen test. We then assessed the contribution of the basal ganglia motor loops to these impairments, using open field testing and analysis of drug-induced locomotor
15-Lipoxygenase-2 (ALOX15B), an oxidoreductase in the metabolism of arachidonic acid, is a functional tumor suppressor whose expression is reduced in a variety of human cancers. To determine the roles of ALOX15B in carcinogenesis, we generated transgenic mice with ALOX8, the murine homolog of ALOX15B, knocked out. ALOX8 expression at mRNA level was abolished in homozygous knockout mice and reduced to half of wild type in heterozygous knockout mice. Its observed that homozygous female ALOX8 knockout mice are infertile but male ALOX8 knockout mice are fertile. Increased incidence of tumor as uni or multimass was found in the lung, prostate and in the mesentery region of homozygous and heterozygous ALOX8 knockout mice, when compared with little mate wild type mice. Histological evaluations showed an increase in secondary tumors and inflammation in different tissues like lung and large intestine in mice with ALOX8 knocked out. The transgenic mice could be a good model to study the role of ...
Our results show an important role for the extracellular matrix molecule TN-C in the regulation of neural precursor cell proliferation and migration, as revealed by reduced proliferation of SVZ cells and OP cells in transgenic mice that lack TN-C (Saga et al., 1992). These mice have previously been reported as normal (Saga et al., 1992). Although subsequent studies have revealed changes in behaviour (Fukamauchi et al., 1996; Kiernan et al., 1999) and neurotransmitter levels (Fukamauchi et al., 1996) in the CNS, as well as abnormalities of neuromuscular junction architecture (Cifuentes-Diaz et al., 1998) and repair in the kidney (Nakao et al., 1998), no developmental abnormalities have been described previously. Our results are therefore important in that they demonstrate for the first time a significant role for TN-C in the basic processes of cell growth control during normal development.. The reduction in cell proliferation in the TN-C-deficient animals was revealed by BrdU studies in vivo, ...
There is growing evidence that neuropeptide Y acting through Y1 and Y2 receptors has a prominent role in modulating anxiety- and depression-like behavior in rodents. However, a role of other Y receptors like that of Y4 receptors in this process is poorly understood. We now investigated male Y2, Y4 single and Y2/Y4 double knockout mice in behavioral paradigms for changes in motor activity, anxiety and depression-like behavior. Y4 and Y2 knockout mice revealed an anxiolytic phenotype in the light/dark test, marble-burying test and motor-activity independent in stress-induced hyperthermia, and reduced depression-like behavior in the forced swim and tail suspension tests. In Y2/Y4 double knockout mice, the response in the light/dark test and in the forced swim test was further enhanced compared to Y4 and Y2 knockout mice, respectively. Motor activity was increased in Y2, Y4 and Y2/Y4 knockout mice under changing and stressful conditions, but not altered in a familiar environment. High levels of Y4 ...
Activation of neuropeptide S (NPS) signaling has been found to produce arousal, wakefulness, anxiolytic-like behaviors, and enhanced memory formation. In order to further study physiological functions of the NPS system, we generated NPS precursor knockout mice by homologous recombination in embryonic stem cells. NPS-/- mice were viable, fertile, and anatomically normal, when compared to their wild-type and heterozygous littermates. The total number of NPS neurons-although no longer synthesizing the peptide - was not affected by the knockout, as analyzed in NPS-/- /NPSEGFP double transgenic mice. Analysis of behavioral phenotypes revealed significant deficits in exploratory activity in NPS-/- mice. NPS precursor knockout mice displayed attenuated arousal in the hole board test, visible as reduced total nose pokes and number of holes inspected, that was not confounded by increased repetitive or stereotypic behavior. Importantly, long-term memory was significantly impaired in NPS-/- mice in the ...
We have previously reported the TCR inhibitory molecule CD5 impairs reactivity of tumor-specific PBL-derived T-cell clones against the cognate target and controls their susceptibility to activation-induced cell death (AICD) triggered by tumor cells. In this report, we compared the antitumor T-cell response developed against the B16F10 melanoma engrafted in CD5-deficient and wild-type (wt) C57BL/6 mice. Our results indicate that CD5 knock out mice elicit a delayed tumor growth as compared to wt mice, which is associated with tumor infiltration by more activated tumor-reactive T lymphocytes. Our data also indicate that tumor suppression in CD5-deficient mice is transient and that tumor flare up correlates with increase in AICD of tumor-infiltrating CD8+ T cells. Our data suggest that tumor T lymphocyte infiltration occurs at early stages of cancer development and that tumor-mediated AICD is most likely involved in the induction of T-cell tolerance to malignant cells. ...
M1 Muscarinic Receptor Knockout: support involvement in cognitive processes.. The five Muscarinic Acetylcholine (ACh) receptors are G-protein coupled receptors (M1R-M5R). M1R, M3R and M5R selectively couple to Gq/G11; M2R and M4R selectively couple to Gi/Go. M1R knockout mice are viable and fertile, and have no major morphological abnormalities.. M1 muscarinic receptors are located in higher brain regions of the central nervous system that are involved in cognitive processes. Studies in M1R knockout mice show that M1 receptors may be involved in cortical memory functions that require interactions between the cerebral cortex and hippocampus. Supporting a role for M1 receptor activation in cognition, muscarinic agonist-induced activation of the MAPK pathway, which plays an important role in synaptic plasticity and many cognitive functions, is virtually abolished in primary cortical cultures or CA1 hippocampal pyramidal neurons in M1R knockout mice. ...
TY - JOUR. T1 - Phospholipase β4-knockout mouse exhibits retinal phenotype. AU - Jiang, Huiping. AU - Lyubarsky, A.. AU - Vardi, N.. AU - Pugh Jr, Edward N. AU - Chen, J.. AU - Xu, J.. AU - Simon, M. I.. AU - Wu, Dianqing. PY - 1996/2/15. Y1 - 1996/2/15. N2 - Purpose: Determine if PLC-β4 has a retinal function by making/assessing a mouse knockout. Rationale: PLC-β4 is one of the four PLC-β isoforms that have been cloned and can be activated by the Gα subunits of G-proteins of the Gq class, but not by the Gβγ subunits. PLC-β4 shares a closer homology to the NorpA protein (which mediates phototransduction in Drosopnila) than to the isoforms PLC-β1-β3. Previous immunohistochemical studies have shown that PLC-β4 is expressed in cone photoreceptors, and in bipolar and ganglion cells1. Method: A mouse line was generated in which the PLC-β4 genes are disrupted. Retinal rod function was assessed with single-flash a- and b-wave electroretinography. Anatomical analysis of rod density, rod ...
Its not every day that you get something useful at no charge. But if youre a researcher studying genes that produce secreted and transmembrane proteins, today is your day. A full 472 knockout mouse lines - all extensively characterized (phenotyped) - are now publicly available from the National Institutes of Healths Mutant Mouse Regional Resource Center (MMRRC) at the University of California, Davis. Distribution of the lines is supported by the National Center for Research Resources (NCRR) and the NIH-funded Knockout Mouse Project (KOMP) repository, operated by UC Davis and the Childrens Hospital Oakland Research Institute in Oakland, Calif. Knockout mouse lines have served as valuable models to study a range of human conditions, from obesity and heart disease to diabetes and substance abuse. In knockout laboratory mice, researchers have inactivated, or knocked out, a gene with an artificial piece of DNA. This helps scientists infer what a gene normally does by understanding what goes ...
Author: Ebinger, M. et al.; Genre: Journal Article; Published in Print: 2005-09; Title: Is testosterone a substrate of P-glycoprotein in abcb1ab knock out mice?
TY - JOUR. T1 - Mamu-A*01/Kb transgenic and MHC Class I knockout mice as a tool for HIV vaccine development. AU - Li, Jinliang. AU - Srivastava, Tumul. AU - Rawal, Ravindra. AU - Manuel, Edwin. AU - Isbell, Donna. AU - Tsark, Walter. AU - La Rosa, Corinna. AU - Wang, Zhongde. AU - Li, Zhongqi. AU - Barry, Peter A. AU - Hagen, Katharine D.. AU - Longmate, Jeffrey. AU - Diamond, Don J.. PY - 2009/4/25. Y1 - 2009/4/25. N2 - We have developed a murine model expressing the rhesus macaque (RM) Mamu-A*01 MHC allele to characterize immune responses and vaccines based on antigens of importance to human disease processes. Towards that goal, transgenic (Tg) mice expressing chimeric RM (α1 and α2 Mamu-A*01 domains) and murine (α3, transmembrane, and cytoplasmic H-2Kb domains) MHC Class I molecules were derived by transgenesis of the H-2KbDb double MHC Class I knockout strain. After immunization of Mamu-A*01/Kb Tg mice with rVV-SIVGag-Pol, the mice generated CD8+ T-cell IFN-γ responses to several known ...
Nmu (Neuromedin U) and Nmus (Neuromedin S) gene double knock-out mice. Nmu KO: Exon 9 of the Nmu gene was replaced with a PGK-neo cassette. Homozygous mutant mice show a increased body weight. Nms KO: Exon 8 of the Nms gene was replaced with a neo cassette. Homozygous mutant mice show no obvious abnormality. Nmu gene knockout mice (RBRC04549), Nms gene knockout mice (RBRC04550 ...
In humans, there are over 400 genetic syndromes that include a hearing loss component, but most of the genes underlying hearing loss syndromes are currently unknown. The knockout mice tested so far in this study represented only about 15 percent of mouse genes, so the researchers estimate that if the entire genome is searched there will be at least 450 genes required for hearing function.. Professor Steve Brown, senior author on the paper and director of British Medical Research Councils Harwell laboratory, said: Importantly, the large number of hearing loss genes identified in this study demonstrates that there are many more genes involved in deafness in mouse and human genomes than we had previously realised.. Our findings identify 52 genes that have previously not been recognised as being critical for hearing. These increase our knowledge of the many genes and molecular mechanisms required for hearing, and also provide a shortlist of new genes to investigate to discover the genetic basis ...
If one parent is a wild-type mouse and the other is a homozygous knockout mouse, their offspring will be heterozygous at the knockout gene. The mouse will likely produce the protein from the wild-type copy of the gene, but depending on how the gene is regulated it is likely that expression of the protein will be below wild-type levels ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
Approach and Results-We bred the macrophage-specific L13a knockout mice L13a Flox+/+ Cre+/+ onto apolipoprotein E-deficient background and generated the experimental double knockout mice L13a Flox+/+ Cre+/+ apolipoprotein E deficient (apoE−/−). L13a Flox+/+ Cre−/− mice on apolipoprotein E-deficient background were used as controls. Control and knockout mice were subjected to high-fat diet for 10 weeks. Evaluation of aortic sinus sections and entire aorta by en face showed significantly higher atherosclerosis in the knockout mice. Severity of atherosclerosis in knockout mice was accompanied by thinning of the smooth muscle cell layer in the media, larger macrophage area in the intimal plaque region and higher plasma levels of inflammatory cytokines. In addition, macrophages isolated from knockout mice had higher polyribosomal abundance of several target mRNAs, thus showing defect in translation control.. ...
Recent Publications. Hill S, Deepa SS, Sataranatarajan K, Premkumar P, Pulliam D, Liu Y, Soto VY, Fischer KE, Van Remmen H. Sco2 deficient mice develop increased adiposity and insulin resistance. Mol Cell Endocrinol. 2017 Nov 5;455:103-14. PMCID:PMC5592144. Sakellariou G, McDonagh B, Porter H, Giakoumaki I, Earl K, Nye G, Vasilaki A, Brooks S, Richardson A, Van Remmen H, McArdle A, Jackson MJ. Comparison of whole body SOD1 knockout with muscle specific SOD1 knockout mice reveals a role for nerve redox signaling in regulation of degenerative pathways in skeletal muscle. Antioxid Redox Signal. 2017 Oct 25. PMID: 29065712. Zhang N, Valentine JM, Zhou Y, Li ME, Zhang Y, Bhattacharya A, Walsh ME, Fischer KE, Austad SN, Osmulski P, Gaczynska M, Shoelson SE, Van Remmen H, Chen HI, Chen Y, Liang H, Musi N. Sustained NFκB inhibition improves insulin sensitivity but is detrimental to muscle health. Aging Cell. 2017 Aug;16(4):847-58. PMCID:PMC5506420. Selected Publications. Masser DR, Clark NW, Van Remmen ...
The ability to genetically modify mice is a powerful tool used in basic and applied research with many applications for the study of gene function and human disease. A current world-wide initiative is generating a knockout mouse strain for every protein coding gene using embryonic stem (ES) cells. Mouse strains and ES cells from these initiatives are made available to the worldwide research community via public repositories.. Once phenotyped, mouse models provide invaluable insights into human gene function with wide-ranging clinical implications, including better understanding of diseases and discovering gene targets for therapeutic agents.. The Embryonic Stem (ES) cell to Mouse (ES2M) service is a core APN facility which provides ready access to the global initiative to discover functional insight for every gene by generating and systematically phenotyping 20,000+ knockout mouse strains. The ES2M service enables Australian researchers to choose the genetically modified ES cell line(s) or mice ...
Sakellariou, GK,McDonagh, B,Porter, H,Giakoumaki, II,Earl, KE,Nye, GA,Vasilaki, A,Brooks, SV,Richardson, A,Van Remmen, H,McArdle, A,Jackson, MJ (2018) Comparison of Whole Body SOD1 Knockout with Muscle-Specific SOD1 Knockout Mice Reveals a Role for Nerve Redox Signaling in Regulation of Degenerative Pathways in Skeletal Muscle. Antioxidants & Redox Signaling, 28 :275-295 [DOI] [Details] ...
PTK787 2HCl and -7 (Lakhani et al. 2006 offers contributed to your knowledge of the physiological tasks of the caspases significantly. Oddly enough C57BL/6 mice deficient for both caspase-3 and -7 perish shortly after delivery while mice missing only caspase-3 or -7 have a normal life span and display a limited apoptotic phenotype in this genetic background (Lakhani et al. 2006 Leonard et al. 2002 This points to the functional redundancy between caspase-3 and -7 during embryogenesis. However several observations suggest that this overlap is not complete and that caspase-3 and -7 also fulfill non-redundant roles in apoptosis. For instance eye lenses of caspase-7 knockout mice are grossly normal whereas those of caspase-3 deficient mice display marked cataracts at the anterior lens pole (Zandy et al. 2005 Further support for this notion stems from biochemical studies demonstrating that caspase-3 and -7 exhibit differential activities toward multiple protein substrates with caspase-7 being more ...
J. K. White, Gerdin, A. - K. , Karp, N. A. , Ryder, E. , Buljan, M. , Bussell, J. N. , Salisbury, J. , Clare, S. , Ingham, N. J. , Podrini, C. , Houghton, R. , Estabel, J. , Bottomley, J. R. , Melvin, D. G. , Sunter, D. , Adams, N. C. , Tannahill, D. , Logan, D. W. , Macarthur, D. G. , Flint, J. , Mahajan, V. B. , Tsang, S. H. , Smyth, I. , Watt, F. M. , Skarnes, W. C. , Dougan, G. , Adams, D. J. , Ramirez-Solis, R. , Bradley, A. , and Steel, K. P. , Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes., Cell, vol. 154, no. 2, pp. 452-64, 2013. ...
In previous studies using a Cdc42GAP knockout, Cdc42 gain-of-activity mouse model, we have shown that constitutively increased Cdc42-GTP species can lead to defective hematopoietic stem/progenitor survival, adhesion, and actin cytoskeleton that may contribute to an engraftment defect in hematopoietic stem/progenitors.20 Cdc42GAP−/− mice also displayed mild anemia and deficiencies in erythroid progenitors. While this animal model provides valuable information for a possible involvement of Cdc42 activity in hematopoiesis, there are inherent weaknesses of the gain-of-activity approach that complicate interpretation of the data as they relate to the physiologic role of Cdc42. For example, this animal model cannot reveal the requirement of Cdc42 in hematopoiesis nor rebut a valid criticism that Cdc42GAP knockout may also bring about Cdc42-independent effects.. To understand the physiological role of Cdc42, we have recently generated a Cdc42-conditional knockout mouse model that uses the loxP/Cre ...
PMID: 32653576 Open Access Edmunds Lia R, Xie Bingxian, Mills Amanda M, Huckestein Brydie R, Undamatla Ramya, Murali Anjana, Pangburn Martha M, Martin James, Sipula Ian, Kaufman Brett A, Scott Iain, Jurczak Michael J (2020) Mol Metab Abstract: PARKIN is an E3 ubiquitin ligase that regulates mitochondrial quality control through a process called mitophagy. Recent human and rodent studies suggest that loss of hepatic mitophagy may occur during the pathogenesis of obesity-associated fatty liver and contribute to changes in mitochondrial metabolism associated with this disease. Whole-body Prkn knockout mice are paradoxically protected against diet-induced hepatic steatosis; however, liver-specific effects of Prkn deficiency cannot be discerned in this model due to pleotropic effects of germline Prkn deletion on energy balance and subsequent protection against diet-induced obesity. We therefore generated the first liver-specific Prkn knockout mouse strain (LKO) to directly address the role of hepatic ...
Caspr3-Deficient Mice Exhibit Low Motor Learning during the Early Phase of the Accelerated Rotarod Task. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Estrogen Receptor-α Knock-Out Mouse Model is an eagle-i resource of type Mus musculus at Charles Drew University of Medicine and Science.
We offer a unique portfolio of transporter humanized and knockout mouse models which can be used for different in vivo applications.
Hus1 inactivation results in abnormal accumulation of γH2AX on autosomes, an extended sex body domain, inclusion of autosomes within the sex body, and X-autoso
The goal of this RFA is to produce the largest number of null mutants possible for the dollars available. NIH recognizes that the dollar figure given in the RFA will demand applicants to propose very aggressive programs that minimize cost while still providing a quality product. We aim to maximize the use of NIH dollars and intend to fund a balanced program that may include a set of applications performing different types of knockout mutations in order to cover as much of the genome as possible with the dollars available. Applicants should propose the best approach they can for accomplishing the goals of maximizing the number of null mutations, cost reduction and quality. The actual balance of the program and costs per knockout will be determined as a result of peer review, Council discussion and staff negotiation with the applicants before funding ...
FUNCTION: This gene encodes a member of the DnaJ or Hsp40 (heat shock protein 40 kD) family of proteins. The encoded protein is a molecular chaperone that stimulates the ATPase activity of Hsp70 heat-shock proteins in order to promote protein folding and prevent misfolded protein aggregation. The encoded protein may also inhibit apoptosis. Peritoneal macrophages derived from homozygous knockout mice for this gene exhibit impaired heat tolerance. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015 ...
Albinism is the best-known of a group of rare genetic disorders that can affect both eyes and skin. Some genes have been identified that are linked to these conditions, but many remain mysterious. Now a team led by UC Davis researchers has identified dozens of these genetic mutations in a screen of gene-targeted knockout mice. The authors hope the work, published Aug. 1 in Scientific Reports, will be a resource for clinicians specializing in genetic disorders.. This mouse data may be of interest to clinicians, especially for patients with no known genetic cause for their condition, said Ala Moshiri, associate professor of ophthalmology in the UC Davis School of Medicine and corresponding author on the paper.. Skin, eyes and nerve tissue are linked because they all develop from the same early embryonic tissue. Another group of rare eye and skin disorders distinct from albinism, called phakomatoses, are also caused by genetic alterations inherited from parents or that occur by accident early ...
Genetic exploration of novel behavioral phenotypes in interleukin-7 and interleukin-18 receptor knockout mice. by Amy F. Eisener-Dorman full download exe or rar online without authorization for free.
Fast delivery of LRRC8B knockout Human Cell Lines for the study of gene function. Created by CRISPR/Cas9 genome editing. Includes matched wildtype control.
Fast delivery of DNMT3B knockout Human Cell Lines for the study of gene function. Created by CRISPR/Cas9 genome editing. Includes matched wildtype control.
Key Points. Endothelial Bmp6 conditional knockout mice exhibit hemochromatosis, whereas hepatocyte and macrophage Bmp6 conditional knockout mice do not.Our data
Safe Knockout to generate both conventional and tissue-specific Knockout mice from a single project, and substantially save time and cost.
Accelerate your research with custom-engineered knockout mouse models. Design your own conditional and constitutive knockout mice or use existing strains.
MyD88-dependent signaling in myo-/fibroblasts (MFs) is involved in epithelial barrier restoration and tolerance. However, the role of MyD88-dependent signaling by MFs in the regulation of inflammatory responses by macrophages in the colonic mucosa is poorly understood. Because colonic MFs respond to MyD88 activation with production of molecules involved in the regulation of macrophages (PGE2, PD-L1, etc.), we hypothesize that MF mediated MyD88 signaling regulates inflammatory responses from macrophages in the colon. Tamoxifen inducible Col1α2Cre Myd88 floxed mice (fibroblast and myofibroblast-specific MyD88 deletion) and α-SMACre MyD88 floxed mice (myo-fibroblast and smooth muscle cell-specific MyD88 deletion) on the same genetic background (C57BL/6) were used in this study. We observed that deletion of MyD88 within MFs resulted in the inflammatory changes and infiltration of lymphocytes within colonic mucosa and moderately aggravated DSS induced acute colitis. Activation of the lymphocyte ...
What is the advantage of knockout over gene therapy in mice model in order to st - posted in General Lab Techniques: Hi, Am going through the literature of TFPI-2 protein, where some people have studied its role in apoE knockout mice by replacing TFPI-2 gene by gene therapy..thereby upregulating its expression, and later also downregulating it via respective vector constructs. Of approximately, 10 years of study of this protein no one introduced any knockout mice...
PANcreatic-DERived Factor (PANDER), or FAM3B, is a 235-amino acid protein strongly expressed within and secreted from the endocrine pancreas. Research surrounding PANDER has revealed a large role for the protein in maintaining glucose homeostasis, as evidenced by several Ad-PANDER overexpressing murine models, our labs pancreas-specific PANDER transgenic overexpressor, and most recently our mixed genetic C57/129J PANDER knockout (PANKO) mouse. However, PANDERs overall role in glycemic regulation and glucose homeostasis has yet to be studied in a purebred C57BL/6J PANDER knockout model. Here we present the first phenotypic characterization of our global PANDER knockout mouse on a C57BL/6J background (PANKO-C57) where we examined metabolics through glucose/insulin tolerance testing, fasting glycemia, and body weights, the concentrations of hormonal analytes along with lipids and corticosterones, and full elucidation of hepatic insulin signaling through the insulin signaling cascade. Overall, the PANKO
Knockout mouse: Knockout mouse, genetically engineered laboratory mouse (Mus musculus) in which a specific gene has been inactivated, or
Approach and Results-SR-BI/LDLR double knockout and control LDLR knockout mice were fed atherogenic diets containing different amounts of fat, cholesterol, and sodium cholate. Double knockout mice fed atherogenic diets high in cholesterol exhibited significantly reduced survival compared with LDLR knockout mice fed the same diets. In addition to increased diet-accelerated aortic sinus atherosclerosis, we observed significant diet-induced CA atherosclerosis in double knockout mice and diet-dependent accumulation of platelets in CA atherosclerotic plaques. This was accompanied by substantial myocardial fibrosis in double knockout mice fed high cholesterol diets. Atherogenic diet fed double knockout mice also exhibited higher circulating cytokine levels, monocytosis with increased proportions of Ly6Chi and Ly6Cint monocytes, and higher adhesion molecule expression in CA endothelial cells compared with control LDLR knockout mice.. ...
Background and aims: Perilipin1 (PLIN1), a lipid droplet-associated protein, plays an important role in the regulation of lipolysis and lipid storage in adipocytes. PLIN1 has recently been reported to be expressed in macrophages within atheroma plaques, suggesting PLIN1 may play a role in the accumulation of lipids at the arterial wall and in the development of atherosclerosis. To clarify the role of PLIN1 in the pathophysiology of atherosclerosis, we assessed the progression of atherosclerosis in PLIN1 transgenic mice (Plin1Tg). Methods: Plin1Tg were crossed with apolipoprotein E knockout mice (ApoeKO). C57BL/6J mice, ApoeKO and Plin1Tg/ApoeKO received a normal chow diet for 20 weeks. Body weight, gonadal fat mass and plasma lipid concentrations were measured. Aortas were collected for quantification of atheroma lesions and histological analysis by Oil Red O staining. Results: Body weight, gonadal adipose mass and plasma triglyceride concentrations were not significantly different among the ...
Mice with homologous disruption of the interferon gamma (IFN-gamma) gene on the C57BL/6 background were infected with Leishmania major and the immune response assessed. In contrast to wild-type or heterozygous knockout mice, deficient animals were unable to restrict growth of the parasite and suffered lethal infection over 6-8 wk. Although wild-type and heterozygous littermates developed CD4+ cells that contained transcripts for IFN-gamma and lymphotoxin, typical of T helper type 1 (Th1) cells, the knockout mice developed CD4+ cells that contained transcripts for interleukin 4 (IL-4), IL-5, and IL-13, typical of Th2 cells. ELISPOT assays confirmed the reciprocal patterns of IFN-gamma or IL-4 production by T cells in similar frequencies in the respective groups of mice, and antibody analysis confirmed the presence of Th2-mediated isotype switching in the knockout mice. These data suggest that CD4+ T cells that normally respond to antigens by differentiation to Th1 cells default to the Th2 pathway ...
TY - JOUR. T1 - Structural and functional abnormalities in the spleen of an mFtz-F1 gene-disrupted mouse. AU - Morohashi, Ken ichirou. AU - Tsuboi-Asai, Hisae. AU - Matsushita, Sumie. AU - Suda, Masahiro. AU - Nakashima, Manabu. AU - Sasano, Hironobu. AU - Hataba, Yoshiaki. AU - Li, Chun Li. AU - Fukata, Junichi. AU - Irie, Junji. AU - Watanabe, Takeshi. AU - Nagura, Hiroshi. AU - Li, En. PY - 1999/3/1. Y1 - 1999/3/1. N2 - The spleen has two main functions. The first is to provide a proper microenvironment to lymphoid and myeloid cells, whereas the second involves clearance of abnormal erythrocytes. Ad4BP/SF-1, a product of the mammalian FTZ-F1 gene (mFTZ-F1), was originally identified as a steroidogenic, tissue- specific transcription factor. Immunohistochemical examination of the mammalian spleens confirmed the expression of Ad4BP/SF-1 in endothelial cells of the splenic venous sinuses and pulp vein. In mFtz-F1 gene-disrupted (KO) mice, several structural abnormalities were detected in the ...
TY - JOUR. T1 - b1-Adrenoceptors compensate for b3-adrenoceptors in ileum from b3-adrenoceptor knock-out mice. AU - Hutchinson, Dana Sabine. AU - Evans, Bronwyn A. AU - Summers, Roger J. PY - 2001. Y1 - 2001. M3 - Article. VL - 132. SP - 433. EP - 442. JO - British Journal of Pharmacology. JF - British Journal of Pharmacology. SN - 1476-5381. IS - 2. ER - ...
Aim: To determine whether high-mobility group box 1 (HMGB1) and Toll like receptor 4 (TLR4) drive the inflammatory cascade that promotes intimal hyperplasia (IH) following acute vascular injury. Methods and Results: Carotid artery wire injury in C57BL/6 mice induced a significant increase in intima to media (I/M) ratio at four weeks. Global deletion of HMGB1 using an inducible knockout mouse strain caused prevention of IH. IH was decreased by over 50% in WT mice treated with HMGB1 neutralizing antibody. Of knockout mouse strains deficient in putative receptors for HMGB1, TLR4-/- mice showed the greatest inhibition of IH. Both anti-HMGB1 treated mice and TLR4-/- mice exhibited a marked decrease in monocytic recruitment. Mice with selective depletion of TLR4 from macrophage exhibited a similar level of inhibition of IH to that seen in the global TLR4-/-. In vitro, dithiol HMGB1 dose-dependently promoted SMC migration and MCP-1/CCR2 expression, which was abolished by TLR4 inhibitory peptide. ...
TY - JOUR. T1 - Analysis of CSK homologous kinase (CHK/HYL) in hematopoiesis by utilizing gene knockout mice. AU - Hamaguchi, Isao. AU - Yamaguchi, Naoto. AU - Suda, Junko. AU - Iwama, Atsushi. AU - Hirao, Atsushi. AU - Hashiyama, Motohiro. AU - Aizawa, Shin Ichi. AU - Suda, Toshio. PY - 1996/7/5. Y1 - 1996/7/5. N2 - CHK/HYL is a non-receptor tyrosine kinase that belongs to CSK (C-terminal Src kinase) family, Northern blotting and RT-PCR analyses showed that CHK/HYL was expressed in large spectrum of hematopoietic cells except for erythroid cells and brain. To explore the function of CHK/HYL in hematopoietic cells, we generated CHK/HYL deficient mice. The mutant mice were apparently normal and fertile, while CSK knockout mice died until E11.5 from a defect in the neural tube formation. Hematological observations including blood counts and FAGS analysis showed no significant abnormalities in CHK/HYL mutant mice. CHK/HYL did not affect the activity of Src, Hck, and Fgr in cultured bone marrow ...
Is it possible to get the striatum astrocyte-specific Cre recombinase-mediated knockout of XX gene knockout mice? Any one understand how to make the knockout locate in striatum or any other good ideas to knockout one gene in one special cell from one..
TY - JOUR. T1 - PKCδ Knockout Mice Are Protected from Dextromethorphan-Induced Serotonergic Behaviors in Mice. T2 - Involvements of Downregulation of 5-HT1A Receptor and Upregulation of Nrf2-Dependent GSH Synthesis. AU - Tran, Hai Quyen. AU - Lee, Youngho. AU - Shin, Eun Joo. AU - Jang, Choon Gon. AU - Jeong, Ji Hoon. AU - Mouri, Akihiro. AU - Saito, Kuniaki. AU - Nabeshima, Toshitaka. AU - Kim, Hyoung Chun. PY - 2018/10/1. Y1 - 2018/10/1. N2 - We investigated whether a specific serotonin (5-HT) receptor-mediated mechanism was involved in dextromethorphan (DM)-induced serotonergic behaviors. We firstly observed that the activation of 5-HT1A receptor, but not 5-HT2A receptor, contributed to DM-induced serotonergic behaviors in mice. We aimed to determine whether the upregulation of 5-HT1A receptor induced by DM facilitates the specific induction of certain PKC isoform, because previous reports suggested that 5-HT1A receptor activates protein kinase C (PKC). A high dose of DM (80 mg/kg, i.p.) ...
Previous studies in male AT2R knockout mice suggest that this receptor contributes to BP control.6 Compared with their wild-type littermates, male AT2R knockout mice exhibit slightly higher systolic BP and induce a more rapid and pronounced increase in BP in secondary models of hypertension, such as volume-expansion-induced hypertension produced by deoxycorticosterone acetate-salt. Controversy exists, however, over the role of the AT2R in modulating the effectiveness of AT1R blockade at lowering BP in male rat models of renin-dependent (eg, 2-kidney, 1-clip) and -independent (eg, the spontaneously hypertensive rat) hypertension, because Ang II hypersensitivity in the absence of the AT2R may simply reflect AT1R upregulation. It is indeed a pity that female AT2R knockouts were not investigated in these studies, because one might predict that they would exhibit an even greater difference in BP and a greater degree of Ang II hypersensitivity compared with their wild-type littermates than the males, ...
Authors: Melissa M Thomas, David C Wang, Donna M DSouza, Matthew P Krause, Andrew S Layne, David S Criswell, Hayley M ONeill, Michael K Connor, Judy E Anderson, Bruce E Kemp, Gregory R Steinberg, Thomas J Hawke
The use of animal models led to great progresses in understanding the role of the endosomal adaptor Lamtor2 in endosomal/lysosomal trafficking. In a first approach LAMTOR2 knockout mice were generated, but severe defects during embryogenesis resulted in no viable offspring (Teis et al., 2006). During this time, 4 patients, all siblings, suffering from a primary immunodeficiency syndrome, due to a hypomorph LAMTOR2 allele, were identified and demanded for further investigations on the function of LAMTOR2 for the immune system (Bohn et al., 2007). Therefore, we have established conditional knockout mouse models to investigate the role of LAMTOR2 for the immune system. A special interest was put on antigen presenting cells including macrophages and dendritic cells (DCs). The correct uptake and processing of pathogens and antigen presentation in the context of the immune response is strictly regulated by the endosomal/lysosomal system. Using a mouse model where Lamtor2 was specifically depleted in ...
Experimental and clinical studies suggest that the vascular endothelium may play an important role in modulating the progression of ventricular and vascular remodeling in heart failure (HF). Impaired endothelium-dependent relaxation caused by decreased endothelial NO has been demonstrated in hypertension and HF in humans and in experimental animals.1,2⇓ NO can be produced by essentially all cell types in the heart and is known to have profound effects on cardiac function. It is synthesized from l-arginine by the catalytic reaction of 3 different isoforms of NO synthase (NOS): neuronal or type 1 NOS (nNOS), inducible or type 2 NOS (iNOS), and endothelial or type 3 NOS (eNOS). nNOS and eNOS are constitutively expressed and Ca2+-dependent enzymes, whereas iNOS is essentially expressed in macrophages and leukocytes in response to appropriate stimuli. All 3 NOS isoforms are expressed in the heart.3 NO is a potent endogenous vasodilator that is responsible for the maintenance of basal vascular tone ...
Animals. The contractile performance was studied in five young (9-14 wk of age) male TR-α1-deficient mice and five wild-type control animals of the same age and weight (28-35 g). The force-frequency relationship (see below) was studied also in muscles from four female TR-α1-deficient mice and four wild-type control mice of the same age and weight. The TR-α1-deficient mice represent a cross between the SV-129/OLa and BALB/c (30). Contractile studies were performed on four male TR-β-deficient (12) and four control mice of the same age and weight as above. This group of mice has a mixed 129/Sv and C57Bl/6J genetic background, and was generated from TR-β+/ − heterozygote backcrosses. The wild-type mice were obtained from crosses of heterozygote TR-α1- or TR-β-deficient mice. The two homozygote wild-type strains were bred in parallel with the respective knockout strains. Thus the knockout strains have the same genetic background as their respective knockout strains: 129/Ola and BALB/c for ...
The purpose of this study was to investigate the hypothesis that cardiomyocyte-specific loss of the electrogenic NBCe1 Na+-HCO3- cotransporter is cardioprotective during in vivo ischemia-reperfusion (IR) injury. An NBCe1 (Slc4a4 gene) cardiac conditional knockout mouse (KO) model was prepared by gene targeting. Cardiovascular performance of wild-type (WT) and cardiac-specific NBCe1 KO mice was analyzed by intraventricular pressure measurements, and changes in cardiac gene expression were determined by RNA Seq analysis. Response to in vivo I/R injury was analyzed after 30 minutes occlusion of the left anterior descending artery followed by 3 hours of reperfusion. Loss of NBCe1 in cardiac myocytes did not impair cardiac contractility or relaxation and caused only limited changes in gene expression patterns, such as those for electrical excitability. However, following ischemia and reperfusion, KO heart sections exhibited significantly fewer apoptotic nuclei than WT sections. These studies indicate that
The GLAST1 knockout mouse is a genetically modified mouse strain in which the gene of this member of the superfamily of the glutamate/aspartate transport proteins has been disrupted. - Italia
This work establishes an impact of cavin‐1 on pressure regulation in the pulmonary circulation. Right ventricular systolic pressure was robustly increased compared to WT littermate controls and accompanied by an increased right ventricular mass and remodeling of airway‐associated blood vessels. Because PAH is a progressive disease and we used younger animals, one may predict a more full‐blown PAH phenotype with aging. Since expression of caveolin‐1 was partly maintained, cavin‐1‐knockout mice may constitute a more adequate model of heritable PAH due to mutations in caveolin‐1 than do caveolin‐1‐knockout mice. This is because the disease‐causing mutations cause a partial reduction of caveolin‐1 (Austin et al. 2012), contrasting with the situation in caveolin‐1‐knockout mice where the protein is completely lacking.. In agreement with our current findings, thicker alveolar septa, hypercellularity, and elevated pulmonary pressure have been reported in ...
The vertebrate spinal cord is composed of billions of neurons and glia cells, which are formed in a highly coordinated manner during early neurogenesis. Specification of these cells at distinct positions along the dorsoventral (DV) axis of the developing spinal cord is controlled by a ventrally located signaling center, the medial floor plate (MFP). Currently, the origin and time frame of specification of this important organizer are not clear. During my PhD thesis, I have analyzed the function of the novel secreted growth factor Midkine-a (Mdka) in zebrafish. In higher vertebrates, mdk and the related factor pleiotrophin (ptn) are widely expressed during embryogenesis and are implicated in a variety of processes. The in-vivo function of both factors, however, is unclear, as knock-out mice show no embryonic phenotype. We have isolated two mdk co-orthologs, mdka and mdkb, and one single ptn gene in zebrafish. Molecular phylogenetic analyses have shown that these genes evolved after two large gene ...
The WT Group provides clients with a single-source engineering solution to help maintain the integrity of all projects from start to finish. With nearly 50 years of experience, WT Groups highly skilled engineering, design and consulting teams ensure consistency, clarity, and accuracy in the most cost and time-efficient manner ...
Several protein-tyrosine phosphatases (PTPs) have been proposed to act as negative regulators of insulin signaling. Recent studies have shown increased insulin sensitivity and resistance to obesity in PTP1B knockout mice, thus pointing to this enzyme as a potential drug target in diabetes. Structure-based design, guided by PTP mutants and x-ray protein crystallography, was used to optimize a relatively weak, nonphosphorus, nonpeptide general PTP inhibitor (2-(oxalyl-amino)-benzoic acid) into a highly selective PTP1B inhibitor. This was achieved by addressing residue 48 as a selectivity determining residue. By introducing a basic nitrogen in the core structure of the inhibitor, a salt bridge was formed to Asp-48 in PTP1B. In contrast, the basic nitrogen causes repulsion in other PTPs containing an asparagine in the equivalent position resulting in a remarkable selectivity for PTP1B. Importantly, this was accomplished while retaining the molecular weight of the inhibitor below 300 g/mol. ...
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We study the molecular alterations of human rhabdomyosarcoma and other musculo-skeletal sarcomas, to dissect the mechanisms leading to unrestricted cell growth and to the inhibition of terminal differentiation. We have also developed a transgenic/knockout mouse that spontaneously develops pelvic rhabdomyosrcomas, allowing the study of early events in the natural history of ...
Transcription regulator protein BACH2 is a protein that in humans is encoded by the BACH2 gene. It contains a BTB/POZ domain at its N-terminus which forms a disulphide-linked dimer and a bZip_Maf domain at the C-terminus. Model organisms have been used in the study of BACH2 function. A conditional knockout mouse line called Bach2tm1a(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Additional screens performed: - In-depth immunological phenotyping - in-depth bone and cartilage phenotyping GRCh38: Ensembl release 89: ENSG00000112182 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000040270 - Ensembl, May 2017 Human PubMed Reference:. Mouse PubMed Reference:. Sasaki S, Ito E, Toki T, Maekawa T, Kanezaki R, Umenai T, Muto A, Nagai H, Kinoshita T, Yamamoto M, Inazawa J, Taketo MM, Nakahata T, Igarashi K, Yokoyama M (Aug 2000). Cloning and expression of human B ...
PHENOTYPE: Homozygous null mice display abnormal T cell numbers, increased T cell proliferation, abnormal cytokine physiology, and decreased susceptibility to experimental autoimmune encephalomyelitis. [provided by MGI curators ...
I am seeking to hire an individual to conduct activities for a lab that is creating animal models of learning and memory -- generating knock-out constructs, as well as, utilizing molecular biology skills to perform Cloning, Plasmid and Phage Preparation, PCR, making cDNA Libraries, Library Screening, Southern and Northern Blot Analyses, Western Blotting. Good communication and organizational skills are a plus. A likely candidate would possess a B.S., M.S. or MD degree. I represent a leading bio-tech company with research facilities in New York and can provide excellent benefits (health insurance, dental, and vision plan, paid vacation and more). A high impact, high profile position with excellent opportunity for advancement. If you know anyone that might be interested please forward this to them or contact: Stan Saxton Voice: 609-584-8733 Ext. 218 Fax: 609-584-9575 E-Mail: sis at candseek.com ...
There is variability in the whole procedure depending largely on the strain from which the stem cells have been derived. Generally cells derived from strain 129 are used. This specific strain is not suitable for many experiments (e.g., behavioural), so it is very common to backcross the offspring to other strains. Some genomic loci have been proven very difficult to knock out. Reasons might be the presence of repetitive sequences, extensive DNA methylation, or heterochromatin. The confounding presence of neighbouring 129 genes on the knockout segment of genetic material has been dubbed the flanking-gene effect.[6] Methods and guidelines to deal with this problem have been proposed.[7][8]. Another limitation is that conventional (i.e. non-conditional) knockout mice develop in the absence of the gene being investigated. At times, loss of activity during development may mask the role of the gene in the adult state, especially if the gene is involved in numerous processes spanning development. ...
Mice have been used as models of human disease because of their physiological and genetic similarities to humans 1. Since the development of the transgenic mouse in 1982 2, numerous manipulations of the mouse genome have been created to ultimately increase the understanding of human cancer. An initial study performed by Donehower et al. 3 introduced a null mutation of the human p53 suppressor gene into a normal p53 gene using homologous recombination. This was performed in mice embryonic stem cells to determine the role of the p53 in tumorigenesis and human malignancies.. The gene encoding p53 is considered a tumor suppressor gene when it appears in its non-mutated form. However, when mutation or deletion of the gene occurs, it is thought to act as an oncogene, inducing the formation of tumors 4. Mutations and loss of the p53 gene have been linked to human tumor formations in a number of organs such as the lung, breast, colon, esophagus, liver, bladder, ovary and brain 5. Findings of p53 gene ...
When bred to mice with a Cre recombinase gene, exon 1 of the targeted gene is deleted in the |i|cre|/i| expressing tissue(s); these conditional knockout mice may be useful in generating early neural progenitor cell-specific mutants. This mutant strain may be useful in studies such as apoptosis in neural development and loss of Notch1 heterozygosity.
T cell emigration from the thymus is essential for immunological homeostasis. While stromal cell-produced sphingosine-1-phosphate (S1P) has been shown to promote thymocyte egress via the S1P receptor, S1PR1, the significance of S1P/S1PR1 signaling in the thymic stromal cells that surround T cells remains unclear. To address this issue, we developed conditional knockout mice (Lyve1-CRE/S1pr1f/f mice) in which S1pr1 was selectively targeted in cells expressing the lymphatic endothelial cell marker, Lyve1. In these mice, T cells were significantly reduced in secondary lymphoid tissues, and CD62L+ mature CD4 and CD8 single-positive (SP) T cells accumulated in the medulla failed to undergo thymus egress. Using a Lyve1 reporter strain in which Lyve1 lineage cells expressed tdTomato fluorescent protein, we unexpectedly found that a considerable proportion of the thymocytes were fluorescently labeled, indicating that they belonged to the Lyve1 lineage. The CD4 and CD8 SP thymocytes in Lyve1-CRE/S1pr1f/f mice
The researchers instead embarked on creating Cre-loxP conditional knock out mice for Ezh2. The technique involves two transgenic mouse strains, one carries Cre, an enzyme, under the control of a B or T cell promoter gene. The other strain, in this case, carries the Ezh2 gene surrounded by a special binding site called loxP. LoxP sites on DNA are recognizable by the Cre enzyme. When Cre mice are bred with mice carrying the loxP surrounded Ezh2 gene, the resulting mice lack Ezh2 gene only in developing B cells. As a result the Ezh2 needed in embryonic development is not deterred in these mice. This in vivo model of studying cell signaling is invaluable ...
SRC-2 coactivator deficiency decreases functional reserve in response to pressure overload of mouse heart.s profile, publications, research topics, and co-authors
CompoZr Zinc Finger Nuclease (ZFN) Technology is a novel system for rapid creation of targeted gene knockouts, genomic insertions or gene editing in eukaryotic systems. ZFNs are highly efficient pairs of custom nucleases designed and made by Sigma-Aldrich to target your gene or genomic sequence of interest. ZFNs (mRNA or plasmid formats) are delivered to cells by transfection methods or to embryos by microinjection. Upon cleavage of the target site, endogenous cellular processes are harnessed to produce targeted mutations that result in gene knockout.
DISC1 mutant mice exhibit greater responses to an NMDA antagonist, MK-801, and D-serine treatment[a] Locomotor activity in open field of male mice before and af
Increased Anxiety-Like Behavior and Enhanced Synaptic Efficacy in the Amygdala of GluR5 Knockout Mice. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
HMIC KO cell line available now. Free of charge wild type control available. Knockout achieved by using CRISPR/Cas9, 1 bp deletion in exon 3 and 28 bp deletion in exon 3.
Erasin KO cell line available now. Free of charge wild type control available. Knockout achieved by using CRISPR/Cas9, Homozygous: 35 bp deletion in exon 1.
These |i| Prkcq|/i| knock-out mice exhibit severely impaired T helper cell (Th2) immune responses as well as abnormal insulin signaling and glucose transport. They are suitable for use in applications related to T cell development, Th2-mediated disease, asthma, and diabetes.
Ako chcem vedieť hlavne ten systém :D Ako je to napr. tak že len chodím na prednášky učiteľ niečo vysvetluje a z toho všetkého vlastne ja potom na kocni semestra robím tú skúšku ? Či on sa ma aj niečo pýta počas prednášok alebo ako to je ?:D Dalej v čom som úplne mimo sú tie kredity :D...Mohol by mi to prosím niekto vysvetliť lebo ja som úplne mimo v tom :D Dík ...
Sakamoto K, Gurumurthy CB, Wagner K (2014), Singh SR, Coppola V (eds.), "Generation of Conditional Knockout Mice", Mouse ... "Generating conditional knockout mice". Transgenic Mouse Methods and Protocols. Methods in Molecular Biology. 693. pp. 205-31. ... Further, these knockouts can be inducible. In several mouse studies, tamoxifen is used to induce the Cre recombinase. In this ... Hall B, Limaye A, Kulkarni AB (September 2009). "Overview: generation of gene knockout mice". Current Protocols in Cell Biology ...
Per2 knockout mice show arrhythmic locomotor activity. The gene ASB1, associated with eveningness and a tendency to day-napping ... In mice, gene ablation of Rgs16 lengthens the circadian period of behavioural rhythm. By temporally regulating cAMP signalling ... Chronotypes have also been investigated in other species, such as fruit flies and mice. Normal variation in chronotype ... "High-fat diet disrupts behavioral and molecular circadian rhythms in mice". Cell Metabolism. 6 (5): 414-421. doi:10.1016/j.cmet ...
"Knockout Mouse Project (KOMP)". The Jackson Laboratory. Retrieved 2017-07-16. Hollander, Anneke I. den; Nishina, Patsy M.; ... and its mice. Worldwide donations of funds and mice allowed the lab to resume operations in 1948. Hosts the Mouse Genome ... The National Institutes of Health (NIH) funds phase 2 of the Knockout Mouse Production and Phenotyping Project (KOMP2). A ... The laboratory is also the world's source for more than 8,000 strains of genetically defined mice, is home of the Mouse Genome ...
Mouse Resources Portal, Wellcome Trust Sanger Institute. "International Knockout Mouse Consortium".[permanent dead link] "Mouse ... A conditional knockout mouse line, called 3010026O09Riktm1a(EUCOMM)Wtsi was generated as part of the International Knockout ... Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta ... Dolgin E (2011). "Mouse library set to be knockout". Nature. 474 (7351): 262-3. doi:10.1038/474262a. PMID 21677718. Collins FS ...
A conditional knockout mouse line, called Cds2tm1a(KOMP)Wtsi was generated as part of the International Knockout Mouse ... Mouse Resources Portal, Wellcome Trust Sanger Institute. "International Knockout Mouse Consortium". Archived from the original ... Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta ... Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262-3. doi:10.1038/474262a. PMID 21677718. Collins ...
A conditional knockout mouse line, called Ikbkaptm1a(KOMP)Wtsi was generated as part of the International Knockout Mouse ... Mouse Resources Portal, Wellcome Trust Sanger Institute. "International Knockout Mouse Consortium". "Mouse Genome Informatics ... Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta ... Dolgin E (June 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262-3. doi:10.1038/474262a. PMID 21677718. ...
Mak, T. W.; Penninger, J. M.; Ohashi, P. S. (2001). "Knockout mice: a paradigm shift in modern immunology". Nature Reviews. ... Lu, Cindy C.; Robertson, Elizabeth J. (1 September 2004). "Multiple roles for Nodal in the epiblast of the mouse embryo in the ... Butler, A. A.; Cone, R. D. (2001). "Knockout models resulting in the development of obesity". Trends in Genetics. 17 (10): S50- ... Conlon, F. L.; Barth, K. S.; Robertson, E. J. (1991). "A novel retrovirally induced embryonic lethal mutation in the mouse: ...
... this is absent from CRH knockout mice). Certain stress responses are abolished in NmU knockout mice. These results suggest that ... In contrast to NmU peptide-deficient mice, NmUR2 knockout (KO) mice appeared normal with regard to stress, anxiety, body weight ... However, the NmUR2 KO mice exhibit reduced pain sensitivity in both hot plate test and the chronic phase of the formalin test. ... ICV injections of NmU in rats and mice induce behavior responses associated with activation of the nociceptive pathways, for ...
VDR knockout mice show more extensive ductal development relative to wild-type mice, as well as precocious mammary gland ... knockout mice or mice treated with the PR antagonist mifepristone show delayed (albeit eventually normal, due to estrogen ... although the ducts remain narrower than those of wild-type mice. In any case, female GHR knockout mice can lactate normally. As ... In addition, VDR knockout has also been shown to result in increased responsiveness of mouse mammary gland tissue to estrogen ...
"Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation". Cell. 98 (4): 437-51. doi:10.1016/S0092-8674(00) ... Distinct Roles in the Control of Wakefulness Demonstrated Using Knock-Out Mouse Models". Journal of Neuroscience. 29 (46): ... "Neuronal activity of histaminergic tuberomammillary neurons during wake-sleep states in the mouse". Journal of Neuroscience. 26 ...
CARM1 knockout mice are smaller and die shortly after birth. CARM1 is required for the epigenetic maintenance of pluripotency ...
Matalon R, Michals-Matalon K, Surendran S, Tyring SK (2006). "Canavan disease: studies on the knockout mouse". N- ... it is possible to induce long-distance axonal regeneration which leads to enhancement of functional recovery in rats and mouse ... "Axons amplify somatic incomplete spikes into uniform amplitudes in mouse cortical pyramidal neurons". PLOS ONE. 5 (7): e11868. ...
Matalon R, Michals-Matalon K, Surendran S, Tyring SK (2006). "Canavan disease: studies on the knockout mouse". N- ... While results in mice have been encouraging (via stem cell transplantation), whether this technique can be effective in ... The shiverer mouse represents one animal model of dysmyelination. Human diseases where dysmyelination has been implicated ... Glycogen synthase kinase 3β inhibitors such as lithium chloride have been found to promote myelination in mice with damaged ...
"Diminished pupillary light reflex at high irradiances in melanopsin-knockout mice". Science. 299 (5604): 245-7. Bibcode:2003Sci ... "Chiasm Formation in Man Is Fundamentally Different from That in the Mouse." Nature.com. Nature Publishing Group, 21 March 2007 ...
He also developed conditional knockout mice based on Cre-Lox recombination. He is one of the founding fathers of the German ...
Cesari F, Rennekampff V, Vintersten K, Vuong LG, Seibler J, Bode J, Wiebel FF, Nordheim A (Feb 2004). "Elk-1 knock-out mice ... Cesari F, Rennekampff V, Vintersten K, Vuong LG, Seibler J, Bode J, Wiebel FF, Nordheim A (2004). "Elk-1 knock-out mice ... and parallel specific modifications of pre-determined RMCE-targets Generation of transgenic knock-out/-in mice and their ... dRMCE therefore appears as a very efficient tool for targeted re-engineering of thousands of mouse alleles produced by the IKMC ...
Hiroaki Kiyokawa's laboratory has shown that Cdc25A knockout mice are not viable. The Cdc25s, and in particular Cdc25A and ... Cdc25B and Cdc25C knockout mice (both single and double mutants) are viable and display no major alterations in their cell ... Ferguson AM, White LS, Donovan PJ, Piwnica-Worms H (April 2005). "Normal Cell Cycle and Checkpoint Responses in Mice and Cells ...
"Dopamine D4 Receptor-Knock-Out Mice Exhibit Reduced Exploration of Novel Stimuli". The Journal of Neuroscience. 19 (21): 9550-6 ... Mice deficient for DRD4 have shown less behavioral responses to novelty. 5HT2A is the serotonin receptor gene. The serotonin 2A ...
Knockout mice and knockout rats have been made with the SB system. Figure 4 illustrates these two uses of SB transposons. For ... Dupuy AJ (August 2010). "Transposon-based screens for cancer gene discovery in mouse models". Semin. Cancer Biol. 20 (4): 261- ... Carlson CM, Largaespada DA (July 2005). "Insertional mutagenesis in mice: new perspectives and tools". Nat. Rev. Genet. 6 (7): ... "Systemic correction of storage disease in MPS I NOD/SCID mice using the sleeping beauty transposon system". Mol. Ther. 17 (7): ...
used a mouse model to cre-lox knockout the Prkar1a gene specifically from cells of the adrenal cortex and observed that the ... "Cushing's Syndrome and Fetal Features Resurgence in Adrenal Cortex-Specific Prkar1a Knockout Mice". PLOS Genetics. 6 (6): ... This mouse KO model phenocopies what happens in human cases of PPNAD. Inactivation of PDE11A4, located at 2q31-5, has also been ... "Loss of Prkar1a leads to Bcl-2 family protein induction and cachexia in mice". Cell Death and Differentiation. 21 (11): 1815-24 ...
Lu X, Ross B, Sanchez-Alavez M, Zorrilla EP, Bartfai T (August 2008). "Phenotypic analysis of GalR2 knockout mice in anxiety- ... findings from galanin transgenic and GAL-R1 knockout mice". Neuropeptides. 39 (3): 239-43. doi:10.1016/j.npep.2004.12.026. PMID ... of 2009 great progress is currently being made in this respect with the generation of receptor subtype-specific knockout mice, ... anticonvulsant in mice, CAS# 367518-31-8 M1145 - selective compared to both GalR1 and GalR3 M1153 - selective compared to both ...
Microarray analysis has shown SH3D21 expression to be decreased in TP63 knockout mice. SH3D21 has been shown to be expressed ... "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine. "SH3D21". Genecards ...
The knockout mice also experienced intention tremors, shorter stride length, and slower swim speed. All of these are symptoms ... The physiological effects of BK channels have been studied extensively using knockout mice. In doing so it was observed that ... there were changes in the blood vessels of the mice. The animals without the BK channels showed increased mean arterial ...
Bonsignore LA, Tooley JG, Van Hoose PM, Wang E, Cheng A, Cole MP, Schaner Tooley CE (2015). "NRMT1 knockout mice exhibit ... "DNA repair kinetics in SCID mice Sertoli cells and DNA-PKcs-deficient mouse embryonic fibroblasts". Chromosoma. 126 (2): 287- ... Tian M, Jones DA, Smith M, Shinkura R, Alt FW (2004). "Deficiency in the nuclease activity of xeroderma pigmentosum G in mice ... Hasty P, Campisi J, Hoeijmakers J, van Steeg H, Vijg J (February 2003). "Aging and genome maintenance: lessons from the mouse ...
TLR11 deficient mice (knockout mouse) are efficiently infected with orally administered Salmonella Typhi. S. Typhi does not ... As noted above, human cells do not express TLR11, but mice cells do. Mouse-specific TLR11 recognizes uropathogenic E.coli and ... For example, a gene coding for a protein analogous to TLR10 in humans is present in mice, but appears to have been damaged at ... Because of this, studies were carried out and it was found that tlr-/- mice can be immunized against S. Typhi and they are used ...
December 1996). "Subregion- and cell type-restricted gene knockout in mouse brain". Cell. 87 (7): 1317-26. doi:10.1016/s0092- ... December 2001). "Deficient neurogenesis in forebrain-specific presenilin-1 knockout mice is associated with reduced clearance ... "Whisker-related neuronal patterns fail to develop in the trigeminal brainstem nuclei of NMDAR1 knockout mice". Cell. 76 (3): ... NIH Blueprint for Neuroscience Research has created several hundreds of Cre driver mouse lines which are currently used by the ...
Groundbreaking new technology has allowed for genetic manipulation and the creation of knockout mice. Scientists genetically ... Crawley, Jaqueline N. (1999). "Behavioural phenotyping of transgenic knockout mice: experimental design and evaluation of ... To reduce memory and learning to its genetic basis, mice can be genetically modified and studied. Generally animal studies ... and hippocampus in DRL performance in mice". Neurobiology of Learning and Memory. 93 (1): 85-91. doi:10.1016/j.nlm.2009.08.007 ...
A similar effect was seen with SLC13A5 (mIndy) knockouts of mice. Cellular biology Rogina B, Reenan RA, Nilsen SP, Helfand SL ( ...
2012). "The mammalian gene function resource: The international knockout mouse consortium". Mammalian Genome. 23 (9-10): 580-6 ... coordinated by the International Knockout-Mouse Consortium, IKMC) with the ultimate goal to have all protein genes mutated via ... Coordinated by the International Knockout Mouse Consortium (IKSC) these ES-cell repositories are available for exchange between ... In the first ("knock-out"-) reaction the gene was tagged with a selectable marker, typically by insertion of a hygtk ([+/-]) ...
"Knockout Mice". Nation Human Genome Research Institute. 2009.. *^ "GM pigs best bet for organ transplant". Medical News Today. ... Gain of function experiments, the logical counterpart of knockouts. These are sometimes performed in conjunction with knockout ... Genetically modified mice are the most common genetically engineered animal model.[88] They have been used to study and model ... In a simple knockout a copy of the desired gene has been altered to make it non-functional. Embryonic stem cells incorporate ...
J. Sprent: Migration and Lifespan of Circulating B-Lymphocytes of Nude (nu/nu) Mice. In: Proc. First Intern. Workshop Nude Mice ... Knockout-Mäuse mit einer Deletion in FOXN1 zeigen den gleichen Phänotyp. Nacktmaus-Weibchen haben unterentwickelte Brustdrüsen ... B. J. Braakhuis u. a.: The potential of the nude mouse xenograft model for the study of head and neck cancer. In: Archives of ... S. Loisel u. a.: Establishment of a novel human B-CLL-like xenograft model in nude mouse. In: Leukemia Research 29/2005, S. ...
"Absence of the SP/SP receptor circuitry in the substance P-precursor knockout mice or SP receptor, neurokinin (NK)1 knockout ... analgesia and aggression in mice lacking the receptor for substance P". Nature. 392 (6674): 394-7. doi:10.1038/32904. PMID ... mice leads to an inhibited cytokine response in granulomas associated with murine Taenia crassiceps infection". The Journal of ...
... mice". PLoS One 4 (1): e4226. PMC 2627485 /journal.pone.0004226 Check ,pmc=. value (juhend). PMID 19156219. ... tuntud kui knockout-hiir) väljatöötamise eest. [33] ... Derived from in Vitro Primordial Germ Cell-like Cells in Mice ...
General gene knock out of the TGF-β resulted in death. Conditional inactivation of TGF-βr2 of osteochondroprogenitor cells in ... Data based on a 10.5-day-old mouse embryo. Included are the multiple factors for differentiation.[2] ... Knock out of the entire pathway results in early embryonic death, therefore most research of this nature utilised conditional ... The disease has symptoms similar to those resulting from Trsp gene knockout.[12] ...
Clinical trials have been conducted on mice using tomatoes expressing antibodies or proteins that stimulate antibody production ...
Knockout mice of the PR have been found to have severely impaired lobuloalveolar development of the mammary glands[17] as well ... "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.. ... Selective ablation of PR-A in a mouse model, resulting in exclusive production of PR-B, unexpectedly revealed that PR-B ... As demonstrated in progesterone receptor-deficient mice, the physiological effects of progesterone depend completely on the ...
In order to achieve a mouse strain that is considered inbred, a minimum of 20 sequential generations of sibling matings must ... guarantees a consistent and uniform animal model for experimental purposes and enables genetic studies in congenic and knock-out ... Systematic inbreeding and maintenance of inbred strains of laboratory mice and rats is of great importance for biomedical ... "Male-male competition magnifies inbreeding depression in wild house mice". Proceedings of the National Academy of Sciences of ...
Studies in y2 knockout mice have shown that they display increased anxiety and depressive-like symptoms in despair based tests ... Other studies with α2 knockout mice have displayed increased anxiety and depression-like symptoms in conflict based feeding ... The mice also had increased corticosterone concentration which is a symptom in major depression in humans. The y2 subunit is ... Additionally, studies in α5 mice showed that the spinal α5-containing GABAA receptor has a minor role in inflammatory pain. An ...
... which could carry the GAR-1 Falcon in addition to Mighty Mouse rockets. The squadron soon upgraded to the F-89J.[19] On 1 ... thus making it more difficult for the Soviet Union to knock out the entire fleet with a surprise first strike.[24] As part of ... These two seat interceptor aircraft were radar equipped and armed with Mighty Mouse rockets. The 412th was also assigned ...
Experiments with strains of mice engineered to remove (knockout) CYP1A1 and CYP1B1 reveal that CYP1A1 primarily acts to protect ... "Basal and inducible CYP1 mRNA quantitation and protein localization throughout the mouse gastrointestinal tract". Free Radic ...
The knockout studies in mice suggested the roles of this kinase in mediating survival signal in T cell development, as well as ... 1996). "The gene encoding protein kinase SEK1 maps to mouse chromosome 11 and human chromosome 17". Genomics. 34 (3): 430-2. ... "Mouse PubMed Reference:". Lin A, Minden A, Martinetto H, Claret FX, Lange-Carter C, Mercurio F, Johnson GL, Karin M (May 1995 ...
Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta ... A conditional knockout mouse line called Sqletm1a(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute. Male and ... Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262-3. doi:10.1038/474262a. PMID 21677718. Collins ... "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337-42. doi:10.1038/ ...
Knockout mice also exhibit cerebellar abnormalities and an increase in the number of sympathetic neurons.[20] ... The phenotype for BDNF knockout mice can be severe, including postnatal lethality. Other traits include sensory neuron losses ... Similar effects could be obtained in BDNF knockout mice, but these effects were reversed by local application of BDNF.[55] This ... "Studies on the physiological role of brain-derived neurotrophic factor and neurotrophin-3 in knockout mice". The International ...
Knockout mice of any SOD enzyme are more sensitive to the lethal effects of superoxide-generating compounds, such as paraquat ... Mice lacking SOD2 die several days after birth, amid massive oxidative stress.[26] Mice lacking SOD1 develop a wide range of ... Knockout or null mutations in SOD1 are highly detrimental to aerobic growth in the budding yeast Saccharomyces cerevisiae and ... Mice lacking SOD3 do not show any obvious defects and exhibit a normal lifespan, though they are more sensitive to hyperoxic ...
Guan, Chunmei; Ye, Chao; Yang, Xiaomei; Gao, Jiangang (2010). "A review of current large-scale mouse knockout efforts". Genesis ... "The Knockout Mouse Project". Nature Genetics 36 (9): 921-924. doi:10.1038/ng0904-921. ISSN 1061-4036. PMC 2716027. PMID ... Georgi, B; Voight, BF; Bućan, M (May 2013). "From mouse to human: evolutionary genomics analysis of human orthologs of ... single-gene knockout mutants: the Keio collection.". Molecular systems biology 2: 2006.0008. doi:10.1038/msb4100050. PMC ...
... and the technique behind gene targeting and knockout mice.[325]. *George Smoot (1945-): American astrophysicist and cosmologist ...
... knockout mice do not acquire compensatory gene expression changes or develop neural lesions over time". Neurobiol. Dis. 14 (1 ... transgenic mouse model of Alzheimer's disease". Neurobiol. Dis. 39 (3): 409-22. PMC 2913404. PMID 20493257. doi:10.1016/j.nbd. ... "The Diabetes Drug Liraglutide Prevents Degenerative Processes in a Mouse Model of Alzheimer's Disease". The Journal of ... "Lipids revert inert Aβ amyloid fibrils to neurotoxic protofibrils that affect learning in mice". EMBO J. 27 (1): 224-33. PMC ...
Another study demonstrated that skeletal muscle fibres of collagen VI knockout mice showed signs of degeneration due to an ... In addition, full knockout of Beclin1 is embryonic lethal whereas knockout of Atg7 or Atg5 is not. ... as mice studies have shown that starvation-induced autophagy was impaired in atg7-deficient mice.[60] ... The study in mice fed with olive oil resulted in an increase in nerve cell autophagy activation compared to controls that had ...
Capecchi, Mario R. (2001). "Generating mice with targeted mutations". Nature Medicine. 7 (10): 1086-90. doi:10.1038/nm1001-1086 ... genetika digunakan untuk mengeluarkan materi genetik dari target maka organisme yang dihasilkan disebut organisme knockout.[12] ... "Simian virus 40 DNA sequences in DNA of healthy adult mice derived from preimplantation blastocysts injected with viral DNA" ...
Another study demonstrated that skeletal muscle fibres of collagen VI knockout mice showed signs of degeneration due to an ... In addition, full knockout of Beclin1 is embryonic lethal whereas knockout of Atg7 or Atg5 is not. ... as mice studies have shown that starvation-induced autophagy was impaired in atg7-deficient mice.[68] ... A study of mice shows that autophagy is important for the ever-changing demands of their nutritional and energy needs, ...
Weissmann C, Flechsig E (2003). "PrP knock-out and PrP transgenic mice in prion research". Br. Med. Bull. 66: 43-60. doi: ... In mice, this same deletion phenotypically varies between Alzheimer's mouse lines, as hAPPJ20 mice and TgCRND8 mice show a ... In the case of direct injection of Aβ oligomers into the hippocampus, PRNP-knockout mice were found to be indistinguishable ... A common approach is using PrP-knockout and transgenic mice to investigate deficiencies and differences.[27] Initial attempts ...
"Opsin activation of transduction in the rods of dark-reared Rpe65 knockout mice". Journal of Physiology. 568 (1): 83-95. doi: ... Lin, Min; Zhang, Min; Abraham, Michael; Smith, Susan M.; Napoli, Joseph L. (2003). "Mouse Retinal Dehydrogenase 4 (RALDH4), ...
"White Matter Damage and the Effect of Matrix Metalloproteinases in Type 2 Diabetic Mice After Stroke". Department of Neurology ... "Effects of matrix metalloproteinase-9 gene knock-out on the proteolysis of blood-brain barrier and white matter components ...
Mice were trained, using foot shocks, to fear a cherry blossom odor. The investigators reported that the mouse offspring had an ... and therefore a single gene knock out is sufficient to cause the disease, where most cases would require both copies to be ... Studies on mice have shown that certain conditional fears can be inherited from either parent. In one example, mice were ... The authors also did not indicate which mice were siblings, and treated all of the mice as statistically independent.[95] The ...
"Adaptation of the myoglobin knockout mouse to hypoxic stress". Am. J. Physiol. Regul. Integr. Comp. Physiol. 286 (4): R786-92. ... "Hypoxia-induced left ventricular dysfunction in myoglobin-deficient mice". American Journal of Physiology. Heart and ...
SAP97's function has been investigated by reducing its expression by knockout or increasing its expression heterologously. Mice ... "Mouse PubMed Reference:".. *^ Müller BM, Kistner U, Veh RW, Cases-Langhoff C, Becker B, Gundelfinger ED, Garner CC (Mar 1995). ... "Discs-large homolog 1 regulates smooth muscle orientation in the mouse ureter". Proceedings of the National Academy of ... "Craniofacial dysmorphogenesis including cleft palate in mice with an insertional mutation in the discs large gene". Molecular ...
3] Navíc AANAT u knockout myšíi vykazuje signifikantně větší dobu její nehybnosti oproti kontrolním myším u modelů deprese na ... N-acetylserotonin promotes hippocampal neuroprogenitor cell proliferation in sleep-deprived mice. Proc. Natl. Acad. Sci. U.S.A. ...
Laboratory work with GMOs classified as low risk, which include knockout mice, are carried out in PC1 lab. This is the case for ...
Alox5 gene knockout mice exhibit an increase in the lung tumor volume and liver metastasis of Lewis lung carcinoma cells that ... Alox5 Gene knockout mice are more susceptible to the development and pathological complications of experimental infection with ... ALOX5 gene knockout mice exhibited a decrease in the number of neutrophils and an increase in the number of bacteria that ... ALOX5 gene knockout mice demonstrate an enhanced resistance and lessened pathology to Brucella abortus infection[31] and, at ...
Knockout mouse, genetically engineered laboratory mouse (Mus musculus) in which a specific gene has been inactivated, or ... Knockout mouse models also give a better understanding of the role of similar genes involved in human diseases. Knockout mouse ... Generation of knockout mice. Technologies used to generate knockout mice include homologous recombination (or gene targeting) ... In order to generate a pair of true knockout mice (homologous knockouts), the mice must be bred over several generations. ...
Completion of a Comprehensive Mouse Knockout Resource: HG-05-007 Frequently Asked Questions (FAQs) *If an applicant is ... I want to propose to make knockouts for a particular gene family. Can I propose to do so under this RFA? No. The RFA calls for ... The actual balance of the program and costs per knockout will be determined as a result of peer review, Council discussion and ... For purposes of consistency, 22,000 genes should be considered the total number of genes in the mouse genome. ...
If one parent is a wild-type mouse and the other is a homozygous knockout mouse, their offspring will be heterozygous at the ... Knockout mice. by cassieconte » Tue Feb 05, 2013 4:54 pm Can someone please explain how it is possible to have a heterozygous ... knock out mouse? If a gene is knocked-out, how can the mouse be heterozygous for the gene? Will the mouse still produce ... If there is some of the protein made, the mouse is a knock-down and not a knock-out. Watch out for the other meaning of ...
Ghanayem, B., Wang, H., & Sumner, S. (2000). Using cytochrome P450 gene knockout mice to study chemical metabolism, toxicity, ... Using cytochrome P450 gene knockout mice to study chemical metabolism, toxicity, and carcinogenicity. ... Using cytochrome P450 gene knockout mice to study chemical metabolism, toxicity, and carcinogenicity ...
C57BL/6 mice. Our results indicate that CD5 knock out mice elicit a delayed tumor growth as compared to wt mice, which is ... CD5 knock out mice display a strong antitumor immune response associated with tumor infiltration by hyperactivated tumor- ... CD5 knock out mice display a strong antitumor immune response associated with tumor infiltration by hyperactivated tumor- ... CD5 knock out mice display a strong antitumor immune response associated with tumor infiltration by hyperactivated tumor- ...
International Knockout Mouse Consortium Knockout Mouse Project (KOMP) Repository North American Conditional Mouse Mutagenesis ( ... The International Knockout Mouse Consortium (IKMC) is a scientific endeavour to produce a collection of mouse embryonic stem ... International Mouse Knockout Consortium (2007). "A mouse for all reasons". Cell. 128 (1): 9-13. doi:10.1016/j.cell.2006.12.018 ... 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337-42. doi: ...
A knockout mouse or knock-out mouse is a genetically modified mouse (Mus musculus) in which researchers have inactivated, or " ... Creating Knockout Mice for Targeting Vector from Knockout Mice Research(KMR) - A website for ordering embryonic stem cells, ... The Knock Out Mouse Project (KOMP) Repository website - The website for ordering ES cells, vectors, and mice generated by the ... There are several thousand different strains of knockout mice.[3] Many mouse models are named after the gene that has been ...
... we generated Cdk2 knockout mice. Surprisingly, these mice are viable, and therefore Cdk2 is not an essential gene in the mouse ... Cdk2 knockout mice are viable.. Berthet C1, Aleem E, Coppola V, Tessarollo L, Kaldis P. ... Although Cdk2 is not an essential gene in the mouse, it is required for germ cell development and meiosis. Loss of Cdk2 affects ... However, Cdk2 is required for germ cell development; both male and female Cdk2(-/-) mice are sterile. Immunoprecipitates of ...
Scientists use FAN1 knockout mice to refine detailed mechanisms involved in damaged DNA repair Like jewels in a vault, our ... genOway to provide EUCOMM conditional knockout mouse models to study human diseases genOway, the biotechnology company ... Researchers identify mutant traits in mouse for many human disease genes About one-third of all genes in the mammalian genome ... New CRISPR-EZ method makes genome editing much easier in mice University of California, Berkeley scientists have developed a ...
Deltagen and Lexicon Knockout Mice The NIH has recently announced an agreement that will allow the distribution of mutant mice ... Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Tumor Biology (MTB), Gene Ontology (GO), MouseCyc ... private collections of knockout mice. These stocks have been created and characterized by Deltagen Incorporated and Lexicon ...
... consortium of researchers report today in Nature that they have knocked out almost 40 percent of the genes in the mouse genome ... A knockout resource for mouse genetics Mouse gene knockout resource will empower mammalian gene studies for a generation ... Program Director of the Knock Out Mouse Program at the National Institutes of Health, a part of the international knockout ... A knockout resource for mouse genetics. Wellcome Trust Sanger Institute. Journal. Nature. Funder. Wellcome Trust Sanger ...
The Knockout Mouse Phenotyping Program (KOMP2) collaborates with the International Mouse Phenotyping Consortium (IMPC) to ... Mouse Data Could Help Wildlife Conservation. Learn how mouse genetic data may help in wildlife conservation efforts ... knockout and characterize all protein-coding genes in the mouse genome. Knocking out the activity of a gene provides valuable ... clues about what that gene normally does but creating mice with gene knockouts is a time-consuming and difficult process, and ...
... to undertake standardized phenotyping of 20,000 knockout mouse strains. The International Mouse Phenotyping Consortium (IMPC) ... The Common Funds Knockout Mouse Phenotyping Program (KOMP2) provides broad, standardized phenotyping of a genome-wide ... Mouse Data Could Help Wildlife Conservation. Learn how mouse genetic data may help in wildlife conservation efforts ... opportunities presented by the large number of mouse mutants generated by global efforts of the International Mouse Knockout ...
Functional muscle analysis of the Tcap knockout mouse.. Markert CD1, Meaney MP, Voelker KA, Grange RW, Dalley HW, Cann JK, ... To provide a model for preclinical trials and for mechanistic studies, we generated knockout (KO) mice carrying a null mutation ... We are the first to establish a viable KO mouse model of Tcap deficiency and our model mice demonstrate a dystrophic phenotype ... and 12-month-old mice. Muscle histology of Tcap-null mice revealed abnormal myofiber size variation with central nucleation, ...
When the researchers tested the bladders of the integrin knockout mice, they found the bladders were constantly squeezing and ... They also found that the mice overfilled their bladders and took much longer to urinate than the normal mice. ... while the second group of mice was normal. Both groups of mice had normal appearing bladders, but the group without the ... The research team tested two groups of mice. One group were genetically modified to be missing an important member of the ...
... the HFE gene knockout mouse has the advantage that only the HFE gene function is disrupted. The β2M knockout mouse also has ... The HFE knockout model we report here resembles the β2M knockout mouse, which also has excessive iron storage, and provided ... 1 A and B). Heterozygous matings of the F1 mice were carried out to produce homozygous F2 mutant mice. Mice were fed with a ... HFE gene knockout produces mouse model of hereditary hemochromatosis. Xiao Yan Zhou, Shunji Tomatsu, Robert E. Fleming, Seppo ...
... Frauke Nitzki,1 Marco Becker,1 Anke Frommhold,1 Walter Schulz-Schaeffer, ... "Ultraviolet and ionizing radiation enhance the growth of BCC and trichoblastomas in Patched heterozygous knockout mice," Nature ... Z. J. Li and C. C. Hui, "BCC and the secret lives of Patched: insights from Patched mouse models," in Basal Cell Carcinoma, V. ... T. Ellis, I. Smyth, E. Riley et al., "Patched 1 conditional null allele in mice," Genesis, vol. 36, no. 3, pp. 158-161, 2003. ...
Mice.. αβγ-Synuclein triple KO mice were maintained on a C57BL6/J background and compared with wild-type C57BL6/J mice ... αβγ-Synuclein triple knockout mice reveal age-dependent neuronal dysfunction. Becket Greten-Harrison, Manuela Polydoro, Megumi ... αβγ-Synuclein triple knockout mice reveal age-dependent neuronal dysfunction. Becket Greten-Harrison, Manuela Polydoro, Megumi ... 2004) Double-knockout mice for alpha- and beta-synucleins: Effect on synaptic functions. Proc Natl Acad Sci USA 101:14966-14971 ...
2007 Nobel Prize in Physiology or Medicine: Knockout Mice. Posted by Nick Anthis on October 8, 2007 ... Since then, the number of reported knockout mouse strains has risen exponentially. Gene targeting has developed into a highly ... Ongoing international efforts will make "knockout mice" for all genes available within the near future. ... all for their work contributing to knockout (and knock-in) mice becoming one of the most powerful scientific tools available to ...
... mice. Before the onset of diabetes, Pdx1 was reduced in islets from Irs2-/- mice, whereas it was expressed normally in islets ... mice. By contrast, transgenic expression of Pdx1 restored β cell mass and function in Irs2-/- mice and promoted glucose ... To investigate whether β cell failure in Irs2-/- mice might be related to dysfunction of MODY-related transcription factors, we ... Whereas male Irs2-/-Pdx1+/+ mice developed diabetes between 8 and 10 weeks of age, haploinsufficiency for Pdx1 caused diabetes ...
... with the help of gene knockout mice from the UC Davis ... Similarly, mice with a genetic knockout of the mouse equivalent ... with the help of gene knockout mice from the UC Davis Mouse Biology Program. The results are published Dec. 18 in the journal ... Knockout mice help find gene for bad breath. December 19, 2017. ScienceBlog.com ... "While we didnt put our noses up to the mices mouths, we did measure high amounts of some of these odor-forming chemicals in ...
Mice. Irs1 knockout (2), Irs2 knockout (2), Pdx1 knockout (8), and wild-type Pdx1 transgene (16) mice were maintained on a ... mice with Pdx1tg mice to increase the Pdx1 gene dosage in the Irs2-/- mice. As previously described, Pdx1tg mice have multiple ... To test the role of Pdx1 in Irs2-/- mice, we intercrossed Irs2+/- mice with Pdx1+/- mice and backcrossed the compound ... mice were slightly smaller by comparison with littermates (Figure 2a). Irs2-/-Pdx1+/- mice and mice lacking Pdx1 (Pdx1-/-, Irs2 ...
... the NIH launched the Knockout Mouse Program (KOMP) to generate knockout (null) mutations in 8,500 genes in C57BL/6 knockout ... 6.I.1. Importation of knockout mice and germplasm. The applicant should describe past and current efforts to import mice from ... collection of mouse knockout mutants, i.e. a library containing a null mutation in every gene in the mouse genome (Austin, C.P ... large-scale knockout efforts in the U.S., with international mouse knockout projects, and with the larger biological research ...
... which allows the one-step generation of conditional knockouts in founder (F0) mice. ... CLICK: one-step generation of conditional knockout mice BMC Genomics. 2018 May 2;19(1):318. doi: 10.1186/s12864-018-4713-y. ... CRISPR with lssDNA inducing conditional knockout alleles), enables the quick generation of floxed alleles in mice and rats. ... which allows the one-step generation of conditional knockouts in founder (F0) mice. ...
Double mutant mice were generated and compared with the single knockouts. Loss of both E2F1 and E2F2 revealed a more striking ... mice. During lactation we noted that E2F3b transcript levels were increased in the E2F2-/- mice. Given that E2Fs have ... QRT-PCR on mammary glands during pregnancy demonstrated increases in E2F2 and E2F3a in the E2F1-/- mice and an increase in E2F2 ... To test this hypothesis, we generated RNA from E2F1-/-, E2F2-/- and E2F3+/- mouse mammary glands. ...
... Roma Pahwa,1,2 Miriam Balderas,3,4 Ishwarlal ... H. Kolb, "Mouse models of insulin dependent diabetes: low-dose streptozocin-induced diabetes and nonobese diabetic (NOD) mice ... S. Devaraj, P. Tobias, B. S. Kasinath, R. Ramsamooj, A. Afify, and I. Jialal, "Knockout of toll-like receptor-2 attenuates both ... I. Jialal, A. M. Major, and S. Devaraj, "Global toll-like receptor 4 knockout results in decreased renal inflammation, fibrosis ...
The amounts of wake and sleep in orexin knock-out mice were nearly normal. Compared with WT littermates, orexin KO mice had the ... We found that orexin KO mice remained awake just as long as WT mice, and their sleep latency was quite similar to WT mice in ... WT mice also have rebound REM sleep, primarily during the dark period. B, Orexin knock-out mice have normal rebound of NREM ... Behavioral State Instability in Orexin Knock-Out Mice. Takatoshi Mochizuki, Amanda Crocker, Sarah McCormack, Masashi Yanagisawa ...
... blood pressure variance was significantly larger in eNOS knockout mice than in controls, and only 2 out of 10 knockout mice had ... During resting conditions, blood pressure variability was markedly enhanced in knockout mice compared with wild-type mice (10.5 ... Statistical comparisons between eNOS knockout mice and wild-type mice were performed by unpaired t tests. ... amount of sequences in the eNOS knockout mice would suggest that the larger blood pressure variability in eNOS knockout mice is ...
Over the past few years, multiple UT knockout mouse models have been generated enabling us to explore the physiological roles ... This review summarizes the new insights of urea transporter functions in different organs from UT knockout mice. Finally, we ... This review summarizes the new insights of urea transporter functions in different organs from UT knockout mice. Finally, we ... Since UT-B has a wide distribution, multiple phenotypic abnormalities were found in UT-B null mice, such as defective urine ...
Knockout Mouse Phenotyping (KOMP2). The NIH Common Fund. Trans-NIH Mouse Initiatives. The NIH Web site for the Knockout Mouse ... Knockout Mouse Phenotyping (KOMP2). The NIH Common Fund. Trans-NIH Mouse Initiatives. The NIH Web site for the Knockout Mouse ... List of Available Knockout Mice [nih.gov]. All knockout lines that have been obtained, with links to how to obtain the mice and ... Knockout Mouse Project Meetings, Papers and News. *Nature News: Mouse Library Set to be Knockout. June 15, 2011 ...
Serotonin-Deficient Knock-out Mouse. Serotonin is an important modulator of many developmental, behavioral, and physiological ... These mice represent a powerful tool for the investigation of behavioral and neuropsychiatric disorders, and development of ... These mice represent a powerful tool for the investigation of behavioral and neuropsychiatric disorders, and development of ...
... say esearchers writing in BMC Neuroscience who applied a battery of behavioral tests to the PKCI/HINT1 knockout animals, ... Mice who had the PKCI/HINT1 gene removed had an anti-depressant-like and anxiolytic-like effect, ... In addition, the knockout mice might be useful as a model to study mania, as there is no other animal model available yet. ... Wang, the corresponding author of the paper, said, "The knockout mice displayed behaviors indicative of changes in mood ...
Fxr2 knockout mice exhibited reduced mGluR-LTD. Furthermore, unlike Fmr1 knockout mice, mGluR-LTD in Fxr2 knockout mice ... Fxr2 knockout, and Fmr1/Fxr2 double knockout mice. Input-output relationship (A) of wild-type, Fmr1 knockout, Fxr2 knockout, ... Fxr2 double knockout mice, but are normal in either Fmr1 knockout or Fxr2 knockout mice. Input-output relationship (A) of wild- ... Fxr2 knockout, and Fmr1/Fxr2 double knockout mice at young ages (4-6 wk old). In addition, Fmr1/Fxr2 double knockout mice ...
Humans share many genes with mice. Consequently, observing the characteristics of knockout mice gives researchers information ... Knockout Mouse - Use. Use. Knocking out the activity of a gene provides information about what that gene normally does. ... Knockout mice also offer a biological and scientific context in which drugs and other therapies can be developed and tested. ... Examples of research in which knockout mice have been useful include studying and modeling different kinds of cancer, obesity, ...
  • Knockout mice exhibit modifications in phenotype (observable traits) and thereby provide important clues about the function of individual genes. (britannica.com)
  • Mice and humans share many genes in common. (britannica.com)
  • Hence, information from knockout mouse models can shed light on the biological roles of specific genes as well as on the involvement of those genes in human disease . (britannica.com)
  • Knockout mouse models also give a better understanding of the role of similar genes involved in human diseases. (britannica.com)
  • The involvement of genes in mammalian organ development and establishment of body plan has been studied thoroughly, owing largely to the development of knockout mice. (britannica.com)
  • For about 15 percent of genes, inactivation via targeted knockout is lethal, preventing altered embryos from developing into adult mice. (britannica.com)
  • Thus, the functions of those genes cannot be studied to the full extent, and their roles in human biology and disease cannot be established through knockout approaches in animals. (britannica.com)
  • What number of genes should an applicant use as the total number of genes in the genome when proposing to generate null mutations in a majority of mouse genes? (genome.gov)
  • For purposes of consistency, 22,000 genes should be considered the total number of genes in the mouse genome. (genome.gov)
  • Method: A mouse line was generated in which the PLC-β4 genes are disrupted. (elsevier.com)
  • We aim to maximize the use of NIH dollars and intend to fund a balanced program that may include a set of applications performing different types of knockout mutations in order to cover as much of the genome as possible with the dollars available. (genome.gov)
  • NPS-/- mice were viable, fertile, and anatomically normal, when compared to their wild-type and heterozygous littermates. (bvs.br)
  • Interestingly, heterozygous littermates often presented behavioral deficits similar to NPS-/- mice or displayed intermediate phenotype . (bvs.br)
  • Here, we analyzed interleukin-7 alpha receptor (Il7r-/-- B6.129S7- Il7rtm1Imx/J) and interleukin-18 alpha receptor (Il18r -/-- B6.129P2-Il18r1tm1Aki/J) knockout/congenic strains to elucidate the genetic underpinnings of learning and memory, ambulation, and anxiety-related behaviors. (mobiletargetmarketing.com)
  • Both approaches involve the use of mouse embryonic stem (ES) cells that are isolated from mouse embryos at about four days following fertilization. (britannica.com)
  • After a few days, the cells are injected into early mouse embryos, which subsequently are implanted into the uterus of a surrogate female, where they eventually develop and are carried to term. (britannica.com)
  • Technologies used to generate knockout mice include homologous recombination (or gene targeting) and gene trapping. (britannica.com)
  • In the first approach, homologous recombination, artificial DNA with flanking sequences that are homologous (identical) to those occurring upstream and downstream of the target gene DNA sequence is introduced into the nucleus of a mouse ES cell. (britannica.com)
  • In order to further study physiological functions of the NPS system, we generated NPS precursor knockout mice by homologous recombination in embryonic stem cells . (bvs.br)
  • Genetic exploration of novel behavioral phenotypes in interleukin-7 and interleukin-18 receptor knockout mice. (mobiletargetmarketing.com)
  • Gene targeting technology necessitates transferring the null mutation from one strain to another- therefore, some genetic material is carried with the gene mutation onto the recipient geneticMoreKnockout mice are widely used in biomedical research. (mobiletargetmarketing.com)
  • This issue complicates knockout studies, but also provides an opportunity for genetic mapping of complex traits. (mobiletargetmarketing.com)
  • Our data show that phenotype differences can result from background genetic differences rather than from loss of the targeted gene in a knockout/congenic strain, as investigators generally assume. (mobiletargetmarketing.com)
  • These studies highlight the importance of investigating the genetic background of knockout mice to avoid misinterpretation of results. (mobiletargetmarketing.com)
  • We therefore generated the first liver-specific Prkn knockout mouse strain (LKO) to directly address the role of hepatic Prkn. (oroboros.at)
  • The foreign DNA typically is engineered to carry a reporter gene, which marks or tags the location of the existing gene, enabling researchers to track its presence in the mouse cell genome as the cells replicate. (britannica.com)
  • However, rather than targeting a specific gene, the foreign DNA is randomly incorporated into any gene in the mouse ES cell genome. (britannica.com)
  • Gene enrichment analyses from liver RNA-seq results suggested significant changes in pathways related to lipid metabolism and fibrosis in HFD-fed Prkn knockout mice. (oroboros.at)
  • Il18r-/- mice exhibit a recessive deficit in ambulatory activity in the open field that does not appear to be influenced by anxiety or physical limitations. (mobiletargetmarketing.com)
  • The total number of NPS neurons -although no longer synthesizing the peptide - was not affected by the knockout, as analyzed in NPS-/- /NPSEGFP double transgenic mice . (bvs.br)
  • Analysis of behavioral phenotypes revealed significant deficits in exploratory activity in NPS-/- mice . (bvs.br)
  • In order to generate a pair of true knockout mice (homologous knockouts), the mice must be bred over several generations. (britannica.com)
  • Knockout mouse , genetically engineered laboratory mouse ( Mus musculus ) in which a specific gene has been inactivated, or "knocked out," by the introduction of a foreign (artificial) DNA sequence. (britannica.com)
  • M1R knockout mice are viable and fertile, and have no major morphological abnormalities. (nih.gov)
  • Using a mouse model of sarcopenia, we're looking specifically at the role of oxidative stress, or free radicals, in the long-term deterioration of muscle. (omrf.org)
  • We also use a mouse model of ALS to study how the loss of an enzyme affects motor neurons. (omrf.org)
  • Knockout animal models also have provided a platform on which to develop and test novel drug therapies. (britannica.com)
  • Furthermore, knocking out a gene may not produce any phenotypic change, and the changes observed in mouse models may be quite different from those observed in humans when the same gene is inactivated in both species. (britannica.com)
  • We utilized a number of transgenic and knockout models with modified antioxidant defense systems to ask whether changes in antioxidant defense and oxidative stress modify lifespan as predicted by the long-standing Oxidative Stress Theory of Aging. (omrf.org)
  • Is testosterone a substrate of P-glycoprotein in abcb1ab knock out mice? (mpg.de)
  • Studies in M1R knockout mice show that M1 receptors may be involved in cortical memory functions that require interactions between the cerebral cortex and hippocampus. (nih.gov)
  • Importantly, long-term memory was significantly impaired in NPS-/- mice in the inhibitory avoidance paradigm. (bvs.br)
  • While there were no differences in mitochondrial content between genotypes on either diet, mitochondrial respiratory capacity and efficiency in liver were significantly reduced in LKO mice. (oroboros.at)
  • Knockout mice exhibit modifications in phenotype (observable traits) and thereby provide important clues about the function of individual genes. (britannica.com)
  • KOMP2 and the NIH Gabriella Miller Kids First Pediatric Research Program (Kids First) are collaborating on a pilot project to develop mouse strains to study, phenotype, and validate coding and noncoding genetic variants (e.g. missense, structural variants, copy number variants, INDELS, frame shifts) identified from Kids First datasets. (nih.gov)
  • We are the first to establish a viable KO mouse model of Tcap deficiency and our model mice demonstrate a dystrophic phenotype comparable to humans with LGMD2G. (nih.gov)
  • The purpose of the Knockout Mouse Phenotyping Project (KOMP2) is to produce a comprehensive resource of null-mutant mice, and associated phenotype data, for the purpose of elucidating functional information for each protein-coding gene in the mammalian genome. (nih.gov)
  • The Data Coordination Center and Database (DCCDB) will perform the curation, analysis, visualization, and dissemination of the phenotype data from the knockout lines. (nih.gov)
  • This age effect in mitochondrial morphology was partially mitigated in 24-month-old p66Shc(-/-) mice, to the extent that both types of mitochondrial populations coexisted in this group (55% tubular mitochondria) showing an intermediate phenotype between 3- and 24-month-old WT mice. (fightaging.org)
  • Now, Shen, Kelleher, and colleagues report that new knock-in mice expressing mutant human PS1 have essentially the same phenotype as older PS1 knockout animals. (alzforum.org)
  • Hewitt K, Pratis K, Jones M, Simpson E. Estrogen replacement reverses the hepatic steatosis phenotype in the male aromatase knockout mouse. (labome.org)
  • This strategy can bypass the limits that are usually observed with constitutive Knockout mouse models (e.g., embryonic lethality, compensatory mechanisms or complex phenotype). (genoway.com)
  • PAP/HIP −/− mice showed the normal phenotype at birth and normal postnatal development. (bmj.com)
  • Our aim was to study Car9-/- knock-out mice brain phenotype using behavioural tests, morphological analysis and microarray. (uta.fi)
  • The premature deletion of Bmi-1 produces a typical osteoporotic phenotype, and Bmi-1 − / − mice have been shown to exhibit a premature aging phenotype of the entire body, including the liver ( 8 ). (spandidos-publications.com)
  • This study aimed at determining the thermoregulatory phenotype of mice lacking transient receptor potential vanilloid-1 (TRPV1) channels. (pubmedcentralcanada.ca)
  • In summary, Trpv1 KO mice possess a distinct thermoregulatory phenotype, which is coupled with a predisposition to age-associated overweight and includes hypometabolism, enhanced skin vasoconstriction, decreased thermopreferendum, and hyperkinesis. (pubmedcentralcanada.ca)
  • By contrast, transgenic expression of Pdx1 restored β cell mass and function in Irs2-/- mice and promoted glucose tolerance throughout life, as these mice survived for at least 20 months without diabetes. (jci.org)
  • The latest advance in antibody technology has arrived in the shape of the Crescendo mouse, a transgenic mouse that is engineered to generate fully human single domain VH fragments. (bioworld.com)
  • RESEARCH DESIGN AND METHODS- To examine adiponectin's contribution to insulin action, we analyzed adiponectin levels and activation of AMP-activated protein kinase (AMPK) in insulin receptor transgenic/knockout mice (L1), a genetic model of resistance to insulin's indirect effects on hepatic glucose production. (diabetesjournals.org)
  • These findings delineate a condition of "adiponectin resistance," previously recognized in IGF-1 receptor dominant-negative transgenic mice ( 21 ), that may contribute to the impairment of insulin's direct control of HGP, as previously reported ( 18 ). (diabetesjournals.org)
  • Transgenic mice expressing human INSR cDNA from the transthyretin ( Ttr ) promoter were intercrossed with Insr +/− mice. (diabetesjournals.org)
  • Here, we subjected male and female 5-HT(3A) knockout mice and their non-transgenic littermates to several tests of social behavior. (uva.nl)
  • Examples of behavioral tasks successfully applied to transgenic and knockout mouse models are provided, as well as references to the primary literature and step-by-step methods protocols. (wiley.com)
  • Behavioral Phenotyping of Transgenic and Knockout Mice, Second Edition has been written in Dr. Crawley's private capacity, outside of her professional position at the National Institutes of Health. (wiley.com)
  • This is an important advance over previous knockout mice, which retain intact lambda light chain: although lambda light chain accounts for at most 10% of the light chains in mouse antibodies, Crescendo believes that knockout of all light chain expression is crucial for the efficient generation of human heavy-chain antibodies in transgenic mice. (drugdiscoverytoday.com)
  • Working with Professor Lluis Montoliu at the Centro Nacional de Biotecnologia in Madrid, transgenic mice have been generated by oocyte microinjection with a first YAC comprising several human V genes, all human D and J genes and a C region engineered for expression in the absence of light chains. (drugdiscoverytoday.com)
  • Transgenic & Knockout Mice protocols describe step-by-step approaches to producing cell and mice with migration related defects. (cellmigration.org)
  • The consortium encompasses four major, high-throughput gene-targeted mutagenesis programs: the National Institutes of Health (NIH)-sponsored Knockout Mouse Program (KOMP) and state-funded Texas Institute for Genomic Medicine (TIGM) in the U.S., the North American Conditional Mouse Mutagenesis (NorCOMM) Program in Canada, and the European Conditional Mouse Mutagenesis (EUCOMM) Programme in Europe. (wikipedia.org)
  • In developing the NIH KOMP plan, this working group considered the current state of the field and recommendations from members of mouse research community made during a second workshop in March 2005. (genome.gov)
  • To request information or products, researchers can call 1-888-KOMP-MICE or e-mail [email protected] . (genome.gov)
  • To serve the KOMP research network laboratories as a central information resource regarding publicly available null and conditional mutants and provide query and display tools to support prioritizing new mouse genes for knockout experiments. (genome.gov)
  • To collect information generated by the KOMP , track progress of the knockout mutant production pipelines, and make the data readily available to all members of the KOMP research network to support, coordinate, and synergize their individual research programs. (genome.gov)
  • To serve as the central public interface for the KOMP , with links to all groups funded by the KOMP research network, as well as link to other efforts generating knockout mice, such as the European and North American Conditional Mouse Mutagenesis programs (EUCOMM and NORCOMM). (genome.gov)
  • For Mice, Cells, and germplasm please contact us at [email protected] , US 1-888-KOMP-MICE or International +1-530-752-KOMP, or for vectors [email protected] or +1-510-450-7917. (komp.org)
  • 8] The goal of KOMP is to create knockout mutations in the embryonic stem cells for each of the 20,000 protein coding genes in mice. (wikipedia.org)
  • These 'triple knockout' mice are believed to be unique. (drugdiscoverytoday.com)
  • Crescendo is now working to generate mice that combine its newly developed YAC and the triple knockout mouse to generate a first-generation Crescendo mouse platform. (drugdiscoverytoday.com)
  • Compared with wild-type (WT) littermates, orexin KO mice had essentially normal amounts of sleep and wake, but wake and non-rapid eye movement (NREM) bouts were very brief, with many more transitions between all behavioral states. (jneurosci.org)
  • However, compared with wild-type littermates, late-phase long-term potentiation (L-LTP) was unaltered in all knockout mice at 4-6 mo of age. (nih.gov)
  • The resulting progeny were further intercrossed to generate Insr −/− and Ttr -INSR (L1) mice and Insr +/+ littermates. (diabetesjournals.org)
  • These knockout mice for p66Shc (p66Shc(-/-)) have been shown to be thinner, to exhibit an increased metabolic rate, and to have less body fat than their wild-type littermates. (fightaging.org)
  • mGluR5 −/− mice and their wild-type littermates were used in our study. (frontiersin.org)
  • mGluR5 −/− mice and wild-type littermates were purchased from Nanjing BioMedical Research Institute of Nanjing University (NBRI). (frontiersin.org)
  • interestingly, PT rates appeared dependent on both CFTR and infection status, with uninfected CFTR +/+ animals demonstrating higher rates of PT than their -/- littermates, while CFTR +/+ P. aeruginosa-infected mice demonstrated lower PT than knockout mice. (ersjournals.com)
  • CB1 knockout mice display increased bone mineral density as compared with normal littermates. (sciencemag.org)
  • In addition, CB1 knockouts were found to eat less than wild-type littermates after temporary food restriction, a behavior linked to the leptin-responsive neural circuitry. (sciencemag.org)
  • In the present study Epac1-/- mice were compared to their reference wild type (WT) littermates, during baseline conditions as well as after per oral water load with and without presence of the antidiuretic vasopressin analog desmopressin. (uib.no)
  • We used Trpv1 knockout (KO) mice and their genetically unaltered littermates to study diurnal variations in deep body temperature ( T b ) and thermoeffector activities under basal conditions, as well as thermoregulatory responses to severe heat and cold. (pubmedcentralcanada.ca)
  • Unresponsiveness to cannabinoids and reduced addictive effects of opiates in CB1 receptor knockout mice. (sciencemag.org)
  • For the past 100 years laboratory mouse genetics have been used for this because mice are mammals that are physiologically similar enough to humans to generate qualitative testing. (wikipedia.org)
  • Methods: ApoE knockout mice (30-week) were exposed to DE (at 200 {mu}g/m{sup 3} of particulate matter) or filtered-air (control) for 7 weeks (6 h/day, 5 days/week). (osti.gov)
  • to discover the wealth of mouse behavioral tasks and to get the guidance you need to select the best methods and necessary controls. (wiley.com)
  • The NIH also awarded cooperative agreements to the University of Pennsylvania in Philadelphia and to the Samuel Lunenfeld Research Institute of Mount Sinai Hospital in Toronto to improve the efficiency of methods for creating knockout lines. (komp.org)
  • Methods: The behavioural analysis for the Car9-/- knock-out mice was done with a slightly modified SHIRPA protocol using wild-type mice as controls. (uta.fi)
  • 9] Some alleles in this project cannot be knocked out using traditional methods and require the specificity of the conditional gene knockout technique. (wikipedia.org)
  • Other combinatorial methods are needed to knockout the last remaining alleles. (wikipedia.org)
  • For example, the p53 knockout mouse is named after the p53 gene which codes for a protein that normally suppresses the growth of tumours by arresting cell division and/or inducing apoptosis. (wikipedia.org)
  • Both groups of mice had normal appearing bladders, but the group without the integrin protein had very little bladder control. (redorbit.com)
  • To address this, we generated and characterized αβγ-synuclein knockout mice, which lack all members of this protein family. (pnas.org)
  • The late onset phenotypes in synuclein null mice were not due to a loss of synapses or neurons but rather reflect specific changes in synaptic protein composition and axonal structure. (pnas.org)
  • Similarly, mice with a genetic knockout of the mouse equivalent of SELENBP1 had low levels of the protein and high levels of methanethiol and other volatile sulfur compounds in their blood. (scienceblog.com)
  • SAP protein is not present in these mice. (taconic.com)
  • Researchers from Karolinska Institutet in Sweden have found a protein that is a critical regulator in the development of fatty liver disease in mice, according to a study published in the journal Nature Communications. (medicalxpress.com)
  • Scientists from the UNC School of Medicine discovered that the anti-inflammatory protein NLRP12 normally helps protect mice against obesity and insulin resistance when they are fed a high-fat diet. (medicalxpress.com)
  • We report that L1 mice display hyperadiponectinemia, associated with the inability to lower plasma glucose levels and blunted hepatic AMP-activated protein kinase (AMPK) response to adiponectin. (diabetesjournals.org)
  • The hepatocytes and adipocytes of the mutant mice failed to accumulate lipid and the expression of the gene for uncoupling protein, the defining marker of brown adipose tissue, was reduced. (sciencemag.org)
  • In this study, we show that special AT-rich sequence binding protein-1 conditional knockout (SATB1cKO) mice, in which the SATB1 gene is specifically deleted from hematopoietic cells, develop SS by 4 wk of age, soon after weaning. (jimmunol.org)
  • The mouse will likely produce the protein from the wild-type copy of the gene, but depending on how the gene is regulated it is likely that expression of the protein will be below wild-type levels. (biology-online.org)
  • If there is some of the protein made, the mouse is a knock-down and not a knock-out. (biology-online.org)
  • In addition, genes encoding tumor necrosis factor (TNF), TNF receptor 2 (TNFR2), and the signaling proteins stress-activated protein kinase (SAPK)/Jun NH 2 -terminal kinase (JNK), were downregulated, and phosphorylated levels of SAPK/JNK/c-Jun were decreased in Retn −/− mice. (diabetesjournals.org)
  • CD4+T cells from microMT mice injected with exogenous protein Ag in adjuvant responded to in vitro challenge by transcription of cytokine mRNA, cytokine secretion, and proliferation. (rupress.org)
  • Peripheral tolerance could be established in microMT mice with a single dose of deaggragated protein. (rupress.org)
  • We generated knockout mice lacking synaptobrevin/VAMP 2, the vesicular SNARE protein responsible for synaptic vesicle fusion in forebrain synapses, to make use of the exquisite temporal resolution of electrophysiology in measuring fusion. (sciencemag.org)
  • However, in comparison between mice and humans, their protein-coding regions of the genomes are 85% identical and have similarities between 99% of their homologs. (wikipedia.org)
  • By causing a specific gene to be inactive in the mouse, and observing any differences from normal behaviour or physiology, researchers can infer its probable function. (wikipedia.org)
  • They are widely used in knockout experiments, especially those investigating genetic questions that relate to human physiology . (wikipedia.org)
  • The first recorded knockout mouse was created by Mario R. Capecchi , Martin Evans , and Oliver Smithies in 1989, for which they were awarded the 2007 Nobel Prize in Physiology or Medicine . (wikipedia.org)
  • Using these mice, we show that synuclein deficiency leads to altered synapse structure and physiology, age-dependent neuronal dysfunction, and impaired survival. (pnas.org)
  • Such gene "knockout" experiments have elucidated the roles of numerous genes in embryonic development, adult physiology, aging and disease. (scienceblogs.com)
  • αβγ-Synuclein triple KO mice lack all murine synucleins and allow us to examine loss-of-synuclein phenotypes while avoiding complications of redundancy and compensation that have limited previous KO analyses of synucleins ( 5 , 20 - 22 ). (pnas.org)
  • Gaia Novarino plans to employ a SETD5 conditional knockout mouse to identify pathophysiological mechanisms underlying ASD and ID phenotypes. (sfari.org)
  • Because SETD5 is expressed in the brain over the course of the entire life, Novarino's group will also assess the temporal development of ASD-related phenotypes in these mice and determine the potential for rescuing behavioral phenotypes in adulthood. (sfari.org)
  • This is supported by the observation that activation of the STAT3/SOCS3 pathway was strongly decreased in the pancreas of PAP/HIP −/− mice and by the reversion of the apoptotic and inflammatory phenotypes upon administration of recombinant PAP/HIP to PAP/HIP −/− mice. (bmj.com)
  • Conditional gene knockouts in mice are often used to study human diseases because many genes produce similar phenotypes in both species. (wikipedia.org)
  • Along with producing similar phenotypes as well making them very promising candidates for conditional gene knockouts. (wikipedia.org)
  • Our Tcap-null mice exhibited a decline in the ability to maintain balance on a rotating rod, relative to wild-type controls. (nih.gov)
  • Before the onset of diabetes, Pdx1 was reduced in islets from Irs2-/- mice, whereas it was expressed normally in islets from wild-type or Irs1-/- mice, which do not develop diabetes. (jci.org)
  • In the present study, we therefore compared blood pressure variability in knockout mice that lack specifically the gene for endothelial nitric oxide synthase with their respective wild-type controls. (ahajournals.org)
  • Four 100-Hz trains evoked L-LTP in wild-type and knockout slices that decayed toward baseline after 3 h. (nih.gov)
  • Here, we describe construction of Lkb1 gene knockout mice and demonstrate that Lkb1 (+/−) mice develop gastrointestinal hamartomas without inactivation of the remaining wild-type Lkb1 allele. (aacrjournals.org)
  • All results were compared with results using wild-type mice expressing normal levels of Cyp7a1 and earlier studies using mixed-background Cyp7a1 knockout mice. (asbmb.org)
  • The mice survived despite their decreased bile acid pool size, which was 40 percent less than in wild-type mice. (asbmb.org)
  • The investigators also noted that the knockout mice showed improved glucose tolerance compared with wild-type mice when fed a normal diet. (asbmb.org)
  • Even on a Western diet, the knockout mice did better in tolerating glucose than wild-type mice. (asbmb.org)
  • They found that the changes in bile acid makeup and glucose tolerance in the knockout mice mimicked the results in wild-type mice. (asbmb.org)
  • Very similar bacterial groups were observed in mGluR5 −/− mice and wild-type controls. (frontiersin.org)
  • In addition, there was no significant difference in the α -diversity of the microbiota between mGluR5 −/− mice and wild-type controls. (frontiersin.org)
  • Though they had less Aβ in the brain than wild-type mice, the heterozygotes had deficits in long- and short-term synaptic plasticity and performed poorly in cognitive tests of spatial memory. (alzforum.org)
  • In this study, gene microarrays were used to screen differentially expressed genes in MOE from AC3 knockout ( AC3 −/− ) and wild-type ( AC3 +/+ ) mice. (mdpi.com)
  • B) Erythrocytes were purified by differential centrifugation from wild-type and cGKIα RM mice. (haematologica.org)
  • Conscious KO and wild-type mice were pulse-labeled with [6- 14 C] glucose during unilateral acoustic stimulation or bilateral acoustic plus whisker stimulation, and label retention was assayed by computer-assisted brain imaging or analysis of [ 14 C]metabolites in extracts, respectively. (wiley.com)
  • 0.05) in inferior colliculus of KO mice, not wild-type mice. (wiley.com)
  • However, there were no labeling differences between KO and wild-type mice for five major HPLC fractions from four dissected regions, presumably because of insufficient anatomical resolution. (wiley.com)
  • Comparing in vitro maturation rate of oocytes, we found oocytes collected from AR −/− mice have a significantly poor maturating rate with 60% reached metaphase II and 30% remained in germinal vesicle breakdown stage, whereas 95% of wild-type AR ( AR +/+ ) oocytes had reached metaphase II. (mdpi.com)
  • No evidence of morphological retinal changes were observed in CaBP1/caldendrin KO and CaBP2 KO mice compared with wild-type mice. (arvojournals.org)
  • However, whole-cell patch clamp recordings of the light responses of alpha-like retinal ganglion cells showed that these light responses in CaBP1/caldendrin KO and CaBP2 KO mice were altered compared with those of wild-type mice. (arvojournals.org)
  • A model of caerulein-induced pancreatitis was used to compare the outcome of pancreatitis in PAP/HIP −/− and wild-type mice. (bmj.com)
  • Caerulein-induced pancreatic necrosis was, however, less severe in PAP/HIP −/− mice than in wild-type mice, as judged by lower amylasemia and lipasemia levels and smaller areas of necrosis. (bmj.com)
  • Bacterial quantification revealed high levels of Staphylococcus xylosus in the corneas of CD36 −/− mice with severe defects, but not in wild-type controls. (arvojournals.org)
  • A knockout mouse or knock-out mouse is a genetically modified mouse ( Mus musculus ) in which researchers have inactivated, or "knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA . (wikipedia.org)
  • Consequently, observing the characteristics of knockout mice gives researchers information that can be used to better understand how a similar gene may cause or contribute to disease in humans. (wikipedia.org)
  • When the researchers tested the bladders of the integrin knockout mice, they found the bladders were constantly squeezing and very overactive. (redorbit.com)
  • An international team of researchers has identified a cause for chronic bad breath (halitosis), with the help of gene knockout mice from the UC Davis Mouse Biology Program. (scienceblog.com)
  • Pure-background knockout mice help researchers better understand bile acid composition. (asbmb.org)
  • The researchers found that their new knockout mouse, when compared with the original knockout mouse, survived better, had higher glucose tolerance and was less likely to develop metabolic disorders. (asbmb.org)
  • This is why the researchers created a Cyp7a1 knockout mouse that had a single genetic background for dietary studies. (asbmb.org)
  • It also reminds researchers to consider genetic background whenever studying mouse models. (asbmb.org)
  • A knockout mouse is a genetically engineered mouse in which researchers have inactivated, or "knocked out," an existing gene by replacing it or disrupting it with an artificial piece of DNA. (avroarrow.org)
  • The researchers propose that loss of PS1 stifled neuronal function independently of Aβ in these mice. (alzforum.org)
  • To find out, the researchers crossed the L435F presenilin knock-in mice with J20 mice , which overexpress mutated human APP and start to develop plaques at around 5 months of age. (alzforum.org)
  • Also, specific bile acids enriched in the pure-background knockout mice may have triggered cellular signaling in the body, causing improved glucose tolerance. (asbmb.org)
  • recently reported that targeting PDK with 2-[(2,4-dihydroxyphenyl)sulfonyl] isoindoline-4,6-diol (designated PS10) resulted in improved glucose tolerance in mice 16 . (nature.com)
  • This award is the final component of a more than $50 million trans-NIH initiative to increase the availability of genetically altered mice and related materials. (komp.org)
  • Millions of knockout mice are used in experiments each year. (wikipedia.org)
  • They did these experiments on a presenilin 2 (PS2) knockout background, because PS2 has been reported to compensate for loss of PS1. (alzforum.org)
  • The results of these experiments indicated that treatment of BKO mice with a moderate dose of PQQ significantly protected the liver from deleterious effects by inhibiting oxidative stress and participating in DNA damage repair. (spandidos-publications.com)
  • Blastocysts containing cells, that are both wildtype and knockout cells, are injected into the uterus of a foster mother. (wikipedia.org)
  • Embryonic stem cells are isolated from a mouse blastocyst (a very young embryo ) and grown in vitro . (wikipedia.org)
  • For this example, we will take stem cells from a white mouse. (wikipedia.org)
  • Artificial DNA sequences typically are introduced into mouse ES cells using a retrovirus or other viral vector, and the modified ES cells are then grown in cell cultures . (britannica.com)
  • The gold-standard method to uncover that role is to mutate a gene in mouse embryonic stem cells: the biochemical and developmental behaviour of the mutated cells can be studied in test tubes or in mice. (eurekalert.org)
  • Or, in the less inspiring Nobel-speak, "for their discoveries of principles for introducing specific gene modifications in mice by the use of embryonic stem cells. (scienceblogs.com)
  • The SAP-deficient mouse model recapitulates several features of XLP: hyperproliferative T cell response following infections, impaired NK and CD8 cell cytotoxicity, defective humoral immune responses, abnormal germinal center formation, reduction in IgG+ memory B cell numbers, and the absence of NKT and other innate T cells. (taconic.com)
  • Genetic deletion of Sorbs2 in mice led to reduced dendritic complexity and decreased frequency of AMPAR-miniature spontaneous EPSCs in dentate gyrus granule cells. (broadinstitute.org)
  • Genetic deletion of Sorbs2 in mice leads to impaired dendritic complexity and reduced excitatory synaptic transmission in dentate gyrus granule cells, accompanied by behavioral deficits in acoustic startle response and long-term memory. (broadinstitute.org)
  • Thus, in mice in which insulin signaling is restricted to liver, selected regions of the brain and pancreatic β-cells (referred to as L1) are, surprisingly, resistant to insulin's direct effect on HGP ( 18 ). (diabetesjournals.org)
  • Recently, it was shown that the 5-HT(3) receptor is also expressed on Cajal-Retzius cells which play a key role in cortical development and that knockout mice lacking this receptor showed aberrant growth of the dendritic tree of cortical layer II/III pyramidal neurons. (uva.nl)
  • Disruption of the Lkb1 gene in mouse ES cells. (aacrjournals.org)
  • To investigate the role of Fgfr1 in neural crest cells, we analyzed Wnt1-Cre;Fgfr1 flox / flox mice. (springer.com)
  • Our results show that specific knockout of Fgfr1 in neural crest cells induced heterotopic chondrogenesis and osteogenesis at the interface of the anterior portions of frontal bones. (springer.com)
  • T cell-dominant immune cell infiltration was observed in the salivary glands of 4 wk old SATB1cKO mice, and the frequency of B cells gradually increased as the mice aged. (jimmunol.org)
  • Transplantation of TGF- beta 1 knockout hematopoietic cells into normal irradiated recipients resulted in a similar profile of autoantibody production as well as in the induction of inflammatory lesions. (bloodjournal.org)
  • Does this imply that all the somatic cells in the mice contain 1 copy of the functional gene and 1 copy of the non-functional gene? (biology-online.org)
  • Each Dicer knockout Mouse embryonic stem cells Lysate is fully covered by our Guarantee+, to give you complete peace of mind and the support when you need it. (novusbio.com)
  • Our Dicer knockout Mouse embryonic stem cells Lysates can be used in a variety of model species. (novusbio.com)
  • The combined collection of mouse ES cells with knockouts in 8,500 genes will be useful for producing knockout mice. (komp.org)
  • The retinal morphology and visual function of six-week-old CaBP1/caldendrin KO and CaBP2 KO mice were analyzed by confocal and electron microscopy and by whole-cell patch-clamp recordings of alpha-like retinal ganglion cells. (arvojournals.org)
  • see " The Plot Thickens on Thin Bones "), whereas cultured osteoclast cells derived from CB1 knockout mice are resistant to the effects of AM251. (sciencemag.org)
  • To test this hypothesis, we allografted either murine B16 melanoma or Lewis lung carcinoma cells into WT and CIB1-KO mice, and monitored tumor growth, morphology, histology, and intra-tumoral microvessel density. (pubmedcentralcanada.ca)
  • Only a few cell types express Cre recombinase and no mammalian cells express it so there is no risk of accidental activation of lox sites when using conditional gene knockout in mammals. (wikipedia.org)
  • p66Shc ablation in mice is translated into a significant decrease in mitochondria-produced ROS and a 30% increase in lifespan. (fightaging.org)
  • On the contrary, pancreas from PAP/HIP −/− mice was more sensitive to apoptosis, in agreement with the anti-apoptotic effect of PAP/HIP in vitro . (bmj.com)
  • The involvement of genes in mammalian organ development and establishment of body plan has been studied thoroughly, owing largely to the development of knockout mice. (britannica.com)
  • Over the past century, the mouse has developed into the premier mammalian model system for genetic research. (avroarrow.org)
  • Here, we show that the electroporation of Cas9, two gRNAs, and long single-stranded DNA (lssDNA) into zygotes, termed CLICK (CRISPR with lssDNA inducing conditional knockout alleles), enables the quick generation of floxed alleles in mice and rats. (nih.gov)
  • Although previous research focused on a Cyp7a1 knockout mouse with a mixed genetic background, the genetically engineered mouse in this report had a pure genetic background. (asbmb.org)
  • Scientists used conditional gene knockout to delete the BRCA1 allele in mammary gland tissue in mice and found that it plays an important role in tumour suppression. (wikipedia.org)
  • Mice lacking Na v 1.7 had much more efficient signaling by the opioid arm, shifting the balance such that the neurons were much less responsive to pronociceptive signals and much more responsive to antinociceptive signals. (sciencemag.org)
  • To provide a model for preclinical trials and for mechanistic studies, we generated knockout (KO) mice carrying a null mutation in the Tcap gene. (nih.gov)
  • I want to propose to make knockouts for a particular gene family. (genome.gov)
  • We hypothesize that PON1 knockout mice develop HHcy that induces MMP-9 expression and causes decreased Akt/ eNOS expression leading to vascular remodeling in atherosclerosis. (ahajournals.org)
  • In a subset of hyperglycemic L1 mice, we observed decreased mRNA expression of AdipoR2 in liver and muscle, as well as decreased peroxisome proliferator-activated receptor (PPAR)α target gene expression in liver, raising the possibility that deterioration of adiponectin/AdipoR2 signaling via PPARα activation contributes to the progression from compensated insulin resistance to diabetes. (diabetesjournals.org)
  • In addition, endothelial nitric oxide is most effective in buffering blood pressure oscillations at frequencies that range from 0.05 to 0.40 s −1 (Hz) in conscious mice. (ahajournals.org)
  • No significant changes in other glutamate receptors or representative synaptic proteins were detected in the prefrontal cortex (PFC) or hippocampus of mGluR5 −/− mice. (frontiersin.org)
  • We derived two cell lines (KHC-1, KHC-2) from the sarcomas of separate mice, and analyzed the levels of STAT family proteins in these cell lines. (aacrjournals.org)
  • Proteins of slots 1 and 5, 2 and 6, 3 and 7, and 4 and 8 were from the same mouse preparation. (haematologica.org)
  • Homologous recombinants were screened and chimeric mice were bred to C57BL6/J mice. (taconic.com)
  • Usp18 knockout mice on a C57Bl6 background developed neurological abnormalities and exhibited 100% mortality within 5 months. (aacrjournals.org)
  • But in the essential step to realize its ambitions of a comprehensive, freely available resource, the team designed and delivered a 'pipeline' that systematically designs and constructs the vectors, and efficiently introduces the engineered DNA molecules into the mouse embryonic stem cell line developed specifically for these projects. (eurekalert.org)
  • The Cftr knockout mouse: This particular strain has helped advance research into cystic fibrosis, the most common fatal genetic disease in the United States today, occurring in approximately one of every 3,300 live births. (avroarrow.org)
  • In this study, we examined whether mucociliary clearance differed between cystic fibrosis (CF) knockout mice and wildtype controls. (ersjournals.com)
  • Measurements were made from uninfected cystic fibrosis transmembrane conductance regulator (CFTR) knockout (-/-) mice and littermate controls (+/+) and compared to measurements from infected animals. (ersjournals.com)
  • These data demonstrate differences in mucociliary clearance between cystic fibrosis transmembrane conductance regulator knockout mice and controls, and further that Pseudomonas aeruginosa infection affects mucociliary clearance in the peripheral airways of mice. (ersjournals.com)
  • Additionally, the observed differences in particle transport suggest that cystic fibrosis transmembrane conductance regulator knockout mice demonstrate different mucociliary responses to infection. (ersjournals.com)
  • Speaking about these results, Wang said, "Although we don't yet know why the deletion of the gene altered the mood status of the mice, what we have learned about the importance of this gene in mood function and its involvement in human mental disorders is interesting. (science20.com)
  • RESULTS- In euglycemic, insulin-resistant L1 mice, we detected hyperadiponectinemia with normal levels of adiponectin receptor-1 and -2. (diabetesjournals.org)
  • 5 In addition, evidence provided by ourselves 3 and Meneton et al 6 indicates that genetically ablating B2R or TK in 129/J mice results in dilated decompensated cardiomyopathy. (ahajournals.org)
  • These results suggest that SATB1cKO mice can be a novel SS model, in which the progression and characteristics of the disease resemble those of human SS. (jimmunol.org)
  • Targeted disruption of the transforming growth factor-beta 1 (TGF-beta 1) gene in mice results in the development of a massive multifocal inflammatory disease in many tissues. (bloodjournal.org)
  • These mice with mixed origin cannot be used for nutritional studies, because the results could be influenced by genes or diet. (asbmb.org)
  • While an explanation for these results is unknown, the authors suspect that fecal bile acid reabsorption from the intestine helped the knockout mice accommodate the relative decline in classic bile acid synthesis. (asbmb.org)
  • Although the negative Western blots did not rule out that the stability of the erythrocytes from cGKI −/− mice might be reduced, these results suggested that the anemia of cGKI −/− mice may be due to a different cause, e.g. bleeding of duodenal ulcers. (haematologica.org)
  • Results: We classified each knockout mouse strain as (1) lighter and smaller, (2) larger and heavier, or (3) the same weight, relative to control mice. (ebscohost.com)
  • Genetic loss of the voltage-gated sodium channel Na v 1.7 (Na v 1.7 −/− ) results in lifelong insensitivity to pain in mice and humans. (sciencemag.org)
  • Results: The behavioural tests showed that Car9-/- knock-out mice were more active in their response tested for locomotor activity, transfer arousal and spontaneous activity. (uta.fi)
  • In the current study we examine the role of homocysteine and its effect on vascular remodeling during atherosclerosis in PON1 knockout mice. (ahajournals.org)
  • PON1 KO mice with atherogenic diet developed atherosclerosis and elevated blood pressures compared to their controls. (ahajournals.org)
  • However, mGluR5 −/− mice exhibited despair-like behaviors following stress exposure. (frontiersin.org)
  • Some studies showed that the antagonists of mGluR5 can effectively alleviate depression-like behaviors in rodents ( 9 ) and that the basal immobility of mGluR5 −/− mice decreased in the forced swim test (FST) ( 9 ) and tail suspension test (TST) ( 1 ). (frontiersin.org)