• 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)
  • 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)
  • Gene knockout in rats is much harder and has only been possible since 2003. (wikipedia.org)
  • A laboratory mouse in which a gene affecting hair growth has been knocked out (left) is shown next to a normal lab mouse. (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)
  • [3] Many mouse models are named after the gene that has been inactivated. (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)
  • White heterozygous mice can subsequently be crossed to produce mice that are homozygous for the knocked out gene. (wikipedia.org)
  • The gene to be knocked out is isolated from a mouse gene library . (wikipedia.org)
  • Usually, the new sequence is also given a marker gene , a gene that normal mice don't have and that confers resistance to a certain toxic agent (e.g., neomycin) or that produces an observable change (e.g. colour or fluorescence). (wikipedia.org)
  • By the natural process of homologous recombination some of the electroporated stem cells will incorporate the new sequence with the knocked-out gene into their chromosomes in place of the original gene. (wikipedia.org)
  • They developed a 'knockout' mouse, in which the gene that codes for Abcc10 was missing, or knocked out. (news-medical.net)
  • The researchers isolated cells from the knockout mice and tested the cells' reactions to taxanes and two other anticancer drugs, vincristine and Ara-C. Compared to cells from normal mice that still possessed the gene for Abcc10, the knockout mouse cells were much more sensitive to the drugs. (news-medical.net)
  • Working with Swaroop, research investigator Alan J. Mears, Ph.D., deleted the gene that makes Nrl in mice, creating an Nrl-knockout strain that developed a retina without rod photoreceptors. (sciencedaily.com)
  • To this end, we currently use several (conditional) knock-out mice and cell lines to study gene expression patterns, metabolic profiles, protein interactions, intracellular trafficking, and signaling pathways. (nih.gov)
  • While the PKD gene products polycystin 1 (PC1) and polycystin 2 (PC2) are known to be essential for establishing and maintaining normal tubule structure, we do not know what they do. (nih.gov)
  • We also do not understand why cysts form immediately after gene inactivation in young mice, but take months to arise in older animals. (nih.gov)
  • To address this issue, we generated E4F knockout mice by gene targeting. (cnrs.fr)
  • Loss of TET2 has been shown to lead to aberrant gene expression that can disrupt normal differentiation processes. (aacrjournals.org)
  • When compared with the human genome it was found that the two genomes were of similar size and almost every gene in the human genome has a counterpart in the mouse. (yourgenome.org)
  • Almost every gene in the human genome has a counterpart in the mouse. (yourgenome.org)
  • Transgenic mice are extremely useful for scientists studying gene function. (yourgenome.org)
  • Whole-body knockout of the Mig6 gene in mice has been shown to induce osteoarthritis and joint degeneration. (bepress.com)
  • These Rnf5 -/ - mice don't show any outward signs of the effects of gene knockout "We call them the 'boring mice' because they don't have a notable phenotype," Ronai commented. (genengnews.com)
  • Pcp2 was first identified as a candidate gene to explain Purkinje cell degeneration in pcd mice (Nordquist, D. T., Kozak, C. A., and Orr, H. T. (1988) J. Neurosci. (embl-heidelberg.de)
  • In this investigation, we considered the effect of PrP gene knock-out (PrP0/0) on cerebellar neural circuits and in particular on granule cells, which show intense PrP expression during development and selective affinity for PrP. (amrita.edu)
  • Adenoviral mediated overexpression of HOXB4 in human primitive hematopoietic cells in vitro generates very high levels of HOXB4 within 24 hours of transduction, leading to an increased differentiation towards myeloid lineages, and to a reduction of primitive hematopoietic progenitors, suggesting that the level of HOXB4 expression may determine the fate options following gene transfer. (dissertations.se)
  • To address this question, we created Treg-specific Cd28 conditional knockout mice. (jci.org)
  • Importantly, the regenerating epithelium around the DUM demonstrated heightened STAT3 phosphorylation and cell proliferation, which was suppressed in uteri of Stat3 conditional knockout mice. (jci.org)
  • This problem has been circumvented with the use of several knockout, knock-in, and overexpressing transgenic mouse models. (molvis.org)
  • We are generating conditional Smurf2 knockout and transgenic mouse models to dissect the precise mechanism of Smurf2-mediated tumor suppression. (umassmed.edu)
  • D and E ) Sorted WT Tregs or Cd28 -ΔTregs were labeled with CellTrace Violet and were stimulated by soluble CD3 plus mitomycin-treated T cell-depleted splenocytes ( D ) with or without rIL-2 or ( E ) with B7-1/B7-2 double-knockout T cell-depleted splenocytes. (jci.org)
  • SV40 immortalized mouse embryonic fibroblasts derived from Bax-Bak double-knockout mice were significantly more resistant to GL-induced cell killing compared with wild-type cells. (aspetjournals.org)
  • We found that Hcrt knock-out mice were unable to work for food or water reward during the light phase. (jneurosci.org)
  • Removing alpha-synuclein in mice (the knock-out mice) also resulted in increased DSBs, following bleomycin treatment. (parkinson.org)
  • Giving healthy human alpha-synuclein to the alpha-synuclein knock-out mice, restored the mice cells' DNA damage response to normal levels. (parkinson.org)
  • Previous studies using nitric oxide synathase (NOS) inhibition, mdx dystrophy mice and NOS-I knock-out mice have suggested that nitric oxide release may mediate satellite cell activation. (cdc.gov)
  • Using HSL knock out mice, we were able to demonstrate that the lipase controls insulin secretion. (lu.se)
  • 4- to 7-week-old WT or Cd28 -ΔTreg mice were pulsed with BrdU every 12 hours for 3 days and sacrificed, and relevant tissues were analyzed by flow cytometry. (jci.org)
  • If we can knock out 70, 80 or 90 percent of tumors without drug accumulation in normal tissues in mice, it is likely that many cancer patients could benefit from this new type of treatment in the long run," Lacko said. (nanowerk.com)
  • Dysregulated autophagy in pancreatic β cells due to hyperglycemia, oxidative stress, and inflammation is associated with diabetes and accompanied by dysregulated autophagy in insulin target tissues and the progression of diabetic complications. (frontiersin.org)
  • Unlike some other tissues, it has not been possible to identify or purify neural stem cells directly from the tissue. (elifesciences.org)
  • COX-1 is expressed constitutively and is isolated throughout most cell lines in almost all mammalian tissues. (medscape.com)
  • Although early studies of IGSF1 ran into roadblocks and blind alleys, armed with the results of detailed clinical investigations, powerful mouse models, and new reagents, the field is now poised to discover IGSF1's function in endocrine tissues, including the pituitary and testes. (medscape.com)
  • There are several thousand different strains of knockout mice. (wikipedia.org)
  • Introduction of several mouse strains with genetic immune deficiencies has greatly benefited the development of a small laboratory animal model ( 7 - 15 ) to study the asexual blood stage infection of P. falciparum . (frontiersin.org)
  • As a result, researchers have been able to develop thousands of mouse strains with mutations that mirror those seen in human genetic disease . (yourgenome.org)
  • Now, there are over 100 different inbred strains of mice, each with a different genetic background. (yourgenome.org)
  • Led by researchers at Sanford Burnham Prebys Medical Discovery Institute, the studies identified a mix of 11 bacterial strains that activated the immune system and slowed melanoma growth in mice. (genengnews.com)
  • METHODS: Using female Sprague Dawley rats, muscle strains were produced by manually stretching (50 repetitions) an activated plantar flexor group through its normal range of motion. (cdc.gov)
  • The team also found that reduced UPR was a common feature in immune and intestinal epithelial cells, and was sufficient for immune cell activation, with studies indicating that altered UPR in Rnf5 -/ - mice was enough to induce changes in both the gut microbiome and immune response. (genengnews.com)
  • All intestinal epithelial cells (IECs) originate from intestinal stem cells (ISCs) that reside in niches of the lower crypt. (researchsquare.com)
  • They are widely used in knockout experiments, especially those investigating genetic questions that relate to human physiology . (wikipedia.org)
  • Therefore, C9-M and C9-C (Rescued phenotype of wild-type growth by genetic complementation) parasites ( 26 ) showed the attenuation in PF13_0027 knock-out parasites (C9-M) growth, which in turn resulted in the irregular cell cycle. (frontiersin.org)
  • For experiments aimed at identifying MYC's synthetic lethal partners, such cells may have advantages over the "immortalized" cells commonly used in cancer research, which contain many genetic alterations that make MYC-specific results difficult to discern. (ucsf.edu)
  • Then, in Goga's UCSF laboratory, thousands of short hairpin RNAs (shRNAs), bits of genetic material that precisely shut down the activity of specific proteins, were sequentially introduced to the engineered cells. (ucsf.edu)
  • Zeroing in on this kinase was encouraging, Goga said, because other researchers have shown that genetic-knockout mice that lack the entire family of PIM kinases are slightly smaller than normal mice, but "basically fine," indicating that a drug targeting just PIM1 may have manageable levels of toxicity in breast cancer patients. (ucsf.edu)
  • In a wild-type genetic background ( mdm2 +/+ ), lens damage and microphthalmia were observed only in mice homozygous for Tg p53 ( t/t ). (molvis.org)
  • Transgenic mice are mice that contain additional, artificially introduced genetic material in every cell. (yourgenome.org)
  • which may render the genetic mate doses of NDMA is the kidney, but a Transplacental carcinogenesis rial of fetal cells highly accessible to much lower incidence of tumours is stu dies with ENU in nonhuman pri carcinogens. (who.int)
  • Th)1 cells.5 Meanwhile, the function and immunity of with genetic predisposition, involving multiple cells, DCs are closely regulated by miRNAs. (cdc.gov)
  • Even though the mice do not have a well-defined macula (a region of the retina that is richer in cones than other parts of the retina), Kellogg researchers hope that this mouse model will allow them to identify the molecules needed for cone function and survival. (sciencedaily.com)
  • As part of the study, researchers also examined the effect of age on cone function in the absence of rods, recording electrical activity in the retina of Nrl knockout mice at different times after birth. (sciencedaily.com)
  • The researchers conducted a series of sophisticated tests in both living mouse brains and human cells to see if this chain of events was taking place. (parkinson.org)
  • Researchers then measured the amount of DSBs in healthy human cells and human cells where alpha-synuclein was completely removed (known as knock-out cells). (parkinson.org)
  • The researchers found that the cells without alpha-synuclein (knock-out cells) had higher levels of DSBs compared to healthy cells, suggesting that alpha-synuclein plays a role in repairing DSBs. (parkinson.org)
  • The researchers report on their findings in a paper titled, " Gut microbiota dependent anti-tumor immunity restricts melanoma growth in Rnf5 -/- mice . (genengnews.com)
  • Researchers first confirmed the distribution of SR-B1 and the uptake of rHDL nanoparticles in mice injected with cancer cells. (nanowerk.com)
  • Mice homozygous for a knock-out allele exhibit normal fertility and Purkinje cell morphology. (jax.org)
  • Furthermore, a knock-in mouse model confirmed that heterozygous or homozygous mutations within Zfp513 (p.R250W) or Kif3c (p.R412H) alone do not led to clear phenotypes with gingival fibromatosis, whereas the double mutations led to gingival hyperplasia phenotypes. (nature.com)
  • These drugs--originally derived from the Pacific yew tree--work by disrupting cell division, thus arresting the growth and spread of tumors. (news-medical.net)
  • The biosynthesis and storage of catecholamines in chromaffin cell tumors may differ from the biosynthesis and storage in the normal medulla. (medscape.com)
  • Initial results demonstrated that melanoma tumors grew more slowly and developed into smaller tumors in Rnf5 -/ - mice than in normal wild-type (WT) mice, and the knockout animals survived for longer. (genengnews.com)
  • 1991. Promotion of mouse lung tumors by bioaccumulated polychlorinated aromatic hydrocarbons. (cdc.gov)
  • Functional malignant cell heterogeneity in pancreatic neuroendocrine tumors revealed by targeting of PDGF-DD. (lu.se)
  • Here, making use of a newly generated Pdgfd knockout mouse, we reveal a functionally important malignant cell heterogeneity modulated by PDGF-DD signaling in pancreatic neuroendocrine tumors (PanNET). (lu.se)
  • The fact that mice lacking the protein have no obvious health problems is encouraging, suggesting that Abcc10 inhibitors could be used in human patients without causing side effects that might be expected to result from interfering with the pump's normal functions. (news-medical.net)
  • The adhesion G-protein-coupled receptor CD97 is present in normal colonic enterocytes but overexpressed in colorectal carcinoma. (nih.gov)
  • A team led by Anand Swaroop, Ph.D., professor of ophthalmology and vision research scientist at the University of Michigan Health System's Kellogg Eye Center, has demonstrated that the retinal protein Nrl is required for rod development and, in fact, acts as a "molecular switch," signaling the cells to develop into rods rather than cones. (sciencedaily.com)
  • The function of this protein in normal cell physiology remains largely unknown. (cnrs.fr)
  • But, because of its physical characteristics and its fundamental role in normal cellular function, MYC has long been considered an "undruggable" protein. (ucsf.edu)
  • To study the potential role in this metabolic shift of von Hippel-Lindau (VHL), a protein component of a ubiquitin ligase complex, the authors generated nephron progenitor cell-specific VHL knockout mice. (lww.com)
  • For example, this may mean the mouse starts to produce a new protein . (yourgenome.org)
  • The induction of proapoptotic Bcl-2 family proteins Bax and Bak and a decrease of antiapoptotic Bcl-2 protein Bcl-2 were observed in GL-treated cells. (aspetjournals.org)
  • The investigations in mouse models indicated a role for the unfolded protein response (UPR) cellular signalling pathway in the ability to hold back cancer growth, while an analysis of human data also identified reduced UPR in melanoma patients who responded to immune checkpoint therapy. (genengnews.com)
  • Work at Ronai's lab has been focused on investigating how cancer responds to stress and becomes resistant to treatment, and their work involves a genetically engineered mouse that lacks the gen for RING finger protein 5 (RNF5), a ubiquitin ligase that helps to remove inappropriately folded or damaged proteins. (genengnews.com)
  • In addition, Paneth cells provide a niche for leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5)-expressing stem cells in crypts (Sato, et al. (researchsquare.com)
  • In heterotrimeric G-protein signalling, cell surface receptors (GPCRs) are coupled to membrane-associated heterotrimers comprising a GTP-hydrolysing subunit G-alpha and a G-beta/G-gamma dimer. (embl-heidelberg.de)
  • Mammalian Purkinje-cell protein-2 (Pcp2). (embl-heidelberg.de)
  • It may function as a cell-type specific modulator for G protein-mediated cell signalling. (embl-heidelberg.de)
  • Interaction of heterotrimeric G protein Galphao with Purkinje cell protein-2. (embl-heidelberg.de)
  • Pcp2 (Purkinje cell protein-2) was identified as a partner for Galphao in this system. (embl-heidelberg.de)
  • Conditional deletion of the Bmi-1 polycomb protein depleted pre-GEPCOT and GEPCOT cells, though pre-GEPCOT cells were more dependent upon Bmi-1 for Cdkn2a ( p16 Ink4a ) repression. (elifesciences.org)
  • Although the role of abnormal prion protein (PrP) conformation in generating infectious brain diseases (transmissible spongiform encephalopathy) has been recognized, the function of PrP in the normal brain remains mostly unknown. (amrita.edu)
  • That's because EF-Tu is a hub protein, interacting with 50 or more other proteins as it carries out its function in the cell. (uncommondescent.com)
  • IGSF1 was localized to thyrotrope cells, implicating the protein in pituitary control of the thyroid. (medscape.com)
  • We show that human and chimpanzee cells differentiate in a similar man¬ner and that the difference in interspecies protein abundance is higher than transcript-level differences, suggesting that post-transcriptional mechanisms play a role in the difference between human and chim¬panzee brain development. (lu.se)
  • TFF3 is predominantly expressed in the goblet cells of the small intestine and colon ( 4 ). (spandidos-publications.com)
  • TET2-knockout mice predominantly develop chronic myelomonocytic leukemia (CMML), but they can also develop other myeloproliferative as well as lymphoproliferative diseases, reflecting the prevalence of TET2 mutations in these varied hematologic malignancies. (aacrjournals.org)
  • Consistent with this notion, we have found that Smurf2-deficient mouse embryonic fibroblasts exhibit delayed senescence entry and enhanced potential to become immortalized in culture, while Smurf2-deficient mice show increased susceptibility to various types of cancer, including B-cell lymphoma, hepatocellular carcinoma, adenocarcinoma in small intestine and soft tissue sarcoma. (umassmed.edu)
  • We procure skin biopsies from patients, reprogram fibroblasts from these into stem cells, i.e., iPSC, which are then differentiated into insulin-producing beta-like cells. (lu.se)
  • huRBC-reconstituted immunodeficient mice received infectious challenge with attenuated P. falciparum C9 parasite mutants (C9-M), complemented (C9-C), and wild type (NF54) progenitors to study the role of immune effectors in the clearance of the parasite from mouse circulation. (frontiersin.org)
  • Nephron progenitors, the self-renewing cells that give rise to nephrons, are particularly metabolically active, relying primarily on glycolysis for energy generation early in development. (lww.com)
  • In addition to identifying VHL as a critical regulator of nephron progenitors' metabolic switching, the authors' findings demonstrate that this switch also plays a large role in the differentiation process, and suggest that VHL is required for normal kidney development. (lww.com)
  • Nephron progenitors, the cell population that give rise to the functional unit of the kidney, are metabolically active and self-renew under glycolytic conditions. (lww.com)
  • To explore VHL as a regulator defining nephron progenitor self-renewal versus differentiation, we bred Six2-TGC tg mice with VHL lox/lox mice to generate mice with a conditional deletion of VHL from Six2 + nephron progenitors. (lww.com)
  • By embryonic day 15.5, kidneys of nephron progenitor cell-specific VHL knockout mice begin to exhibit reduced maturation of nephron progenitors. (lww.com)
  • VHL knockout nephron progenitors also exhibit persistent Six2 and Wt1 expression, as well as decreased mitochondrial respiration and prolonged reliance on glycolysis. (lww.com)
  • 2005). Furthermore, in secretory cell lineages, Gfi1 functions to select goblet/Paneth versus enteroendocrine progenitors (Shroyer, et al. (researchsquare.com)
  • Genomic studies have uncovered silencing TET2 mutations in B-cell and T-cell lymphomas ( 6-8 ), indicating a tumor suppressor role for TET2 in lymphoid malignancies. (aacrjournals.org)
  • Senescence limits proliferative capacity of cells and thus impedes the accumulation of multiple mutations necessary for tumorigenesis. (umassmed.edu)
  • ISCs give rise to transient amplifying cells that become progenitor cells positioned at the bottom two-thirds of the crypts (Barker and Clevers, 2007). (researchsquare.com)
  • The activation of Notch signaling targets Hes-1 and Math-1 differentiates the early progenitor cells into absorptive cells and secretory cell lineages, respectively, in IECs (Fre, et al. (researchsquare.com)
  • Neurons that arise in the adult nervous system originate from neural stem cells and neural progenitor cells. (elifesciences.org)
  • Neural stem cells can also give rise to neural progenitor cells, which proliferate rapidly during their short lives and then 'differentiate' into neurons or glia. (elifesciences.org)
  • Consequently, neural stem and progenitor cells have usually been studied retrospectively, based on their ability to form colonies in laboratory cell cultures. (elifesciences.org)
  • A region of the brain called the subventricular zone contains both neural stem cells and neural progenitor cells, and is one of only two regions of the brain where neural stem cells are found in adult mammals. (elifesciences.org)
  • Firstly, we present a robust 2-week protocol for the differentiation of human pluripotent stem cells (PSCs) into forebrain neural progenitor cells. (lu.se)
  • CRT aims to replace neurons that have degenerated in PD, with donor cells that have the potential to functionally re-integrate into the host circuitry. (lu.se)
  • In paper №2, I describe how mesDA neurons transplanted in the adult SN of a PD mouse model, extended axons across millimetres into the striatum, functionally reforming the nigrostriatal pathway. (lu.se)
  • Eye phenotype and lens histology and ultrastructure were analyzed in adult mice. (molvis.org)
  • Besides impairing ATP production by compromising the normal function of the respiratory chain machinery, excessive ROS generation and the ensuing oxidative stress cause oxidative damage to proteins, lipids, and DNA, accelerating the aging phenotype [ 5 , 6 ]. (aging-us.com)
  • 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)
  • The mouse is closely related to humans with a striking similarity to us in terms of anatomy, physiology and genetics. (yourgenome.org)
  • The involvement of autophagy in the development of diabetes is corroborated by affecting the physiology and role of pancreatic β cells and the homeostasis of glucose. (frontiersin.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)
  • The new sequence from step 1 is introduced into the stem cells from step 2 by electroporation . (wikipedia.org)
  • During development, retinal stem cells differentiate into photoreceptors in response to external and internal cues. (sciencedaily.com)
  • In addition, because the precursor, or stem, cells that give rise to rods and cones experience delays before expressing a specific cell type, there must be some additional cues that signal rod differentiation. (sciencedaily.com)
  • Swaroop explains that if scientists can understand these cues, they may eventually be able to guide the stem cells in the diseased retina of an adult eye to generate new rods. (sciencedaily.com)
  • These clumping proteins are called Lewy Bodies that can be found in an area of the brain stem where dopamine cells die. (parkinson.org)
  • Work in knockout mouse models has shown that TET2 loss enhances hematopoietic stem cell (HSC) self-renewal, expanding the HSC pool (reviewed in refs. (aacrjournals.org)
  • A second method involves introducing the transgenic DNA into embryonic stem cells (ES cells) derived from a mouse embryo at the very early stages of development. (yourgenome.org)
  • These early stem cells have the potential to become any cell type when introduced into another embryo . (yourgenome.org)
  • The embryonic stem cells need a host embryo in which to develop and this is isolated usually from a mouse with different colour fur. (yourgenome.org)
  • Several anti-diabetic strategies including adiponectin, ezetimibe, liraglutide, taurine, adipose tissue-derived stem cells (ADSCs) and even exercise as well as natural products such GABA tea, geniposide, guava extract, vitamin D have been shown to target autophagy. (frontiersin.org)
  • Neurosphere formation is commonly used as a surrogate for neural stem cell (NSC) function but the relationship between neurosphere-initiating cells (NICs) and NSCs remains unclear. (elifesciences.org)
  • Pre-GEPCOT cells could not form neurospheres but expressed the stem cell markers Slc1a3-CreER T , GFAP-CreER T2 , Sox2 CreERT2 , and Gli1 CreERT2 and were long-lived in vivo. (elifesciences.org)
  • Neural stem cells have long lives, much of which they spend in a quiescent state. (elifesciences.org)
  • Since neurosphere-forming cells can self-renew and differentiate into neurons and glia, the ability of cells to form neurospheres has generally been taken as evidence that they are stem cells. (elifesciences.org)
  • However, the exact relationship between neural stem cells and neurosphere-forming cells has been uncertain. (elifesciences.org)
  • have used a technique called flow cytometry to identify and isolate neural stem cells and neurosphere-forming cells directly from the subventricular zone. (elifesciences.org)
  • The neural stem cells, which Mich, Signer et al. (elifesciences.org)
  • These results demonstrate that the cells that form neurospheres in culture are not stem cells at all, and that real stem cells are not able to form colonies under existing culture conditions. (elifesciences.org)
  • Several HOX transcription factors, including HOXB4, are highly expressed in hematopoietic stem cells (HSCs) but are downregulated upon differentiation towards more mature progeny cells. (dissertations.se)
  • The human-induced pluripotent stem cells derived cardiomyocytes (hiPSC-CMs), monoculture cardiac organoids (MCOs) and self-organized cardiac organoids (SCOs) were used in the study. (bvsalud.org)
  • Our most recent initiative is having established a platform for induced pluripotent stem cells (iPSC). (lu.se)
  • A potentially pre-clinical aspect of this thesis is detailed in paper №4 where I describe a robust protocol for the generation of functional mesDA neurons from human embryonic stem cells that are functional in a rat model of PD. (lu.se)
  • Humans share many genes with mice. (wikipedia.org)
  • Our focus is to understand how these genes are involved in the establishment of normal tubular diameter and how their inactivation leads to cyst formation. (nih.gov)
  • He could then use these mice to investigate which genes were responsible for that charact. (yourgenome.org)
  • Tumorigenesis is a multi-step process in which a normal cell acquires changes in a number of critical cancer causing genes. (umassmed.edu)
  • The insulin-producing cells that we can make from these patients can then be used to understand the mechanisms by which these risk genes cause dysfunction of beta-cells. (lu.se)
  • In this issue of Cancer Discovery , Dominguez and colleagues report that TET2 function is critical for germinal center exit and plasma cell differentiation, and its deficiency can lead to B-cell lymphoma phenotypes. (aacrjournals.org)
  • 2008). Lgr5 deficiency leads to premature Paneth cell differentiation in the small intestine without detectable effects on the differentiation of other cell lineages, or on proliferation or migration (Garcia, et al. (researchsquare.com)
  • Studies in our knockout mice reveal that deficiency of HOXB4 leads to a hypocellularity in hematopoietic organs and impaired proliferative capacity. (dissertations.se)
  • We showed how insulin deficiency in Friedreich's ataxia is likely to evolve, and that a mouse model for Huntington's disease develops diabetes due to loss of beta-cells. (lu.se)
  • Investigations in two IGSF1 knockout mouse models converged to show that IGSF1 deficiency leads to reduced expression of the receptor for thyrotropin-releasing hormone (TRH) and impaired TRH stimulation of thyrotropin secretion, providing a candidate mechanism for the central hypothyroidism observed in patients. (medscape.com)
  • Insulin is known to regulate pancreatic β-cell function through the activation of cell surface insulin receptors, phosphorylation of insulin receptor substrate (IRS)-1 and -2, and activation of phosphatidylinositol (PI) 3-kinase. (diabetesjournals.org)
  • 1999. Transactivation activity of human, zebrafish, and rainbow trout aryl hydrocarbon receptors expressed in COS-7 cells: Greater insight into species differences in toxic potency of polychlorinated dibenzo- p -dioxin, dibenzofuran, and biphenyl congeners. (cdc.gov)
  • After seeing the effects on white blood cells, we decided to look at the tissue types that produce white blood cells to see if we could actually see differences there,' says Hopper-Borge. (news-medical.net)
  • I'm a breast oncologist, and I've seen too many patients die from triple-negative disease," said senior author Andrei Goga , MD, PhD, professor of cell and tissue biology and of medicine at UCSF, and a member of the Helen Diller Family Comprehensive Cancer Center. (ucsf.edu)
  • p53 participates in relevant aspects of cell biology, including apoptosis and cell cycle control and must be strictly regulated to maintain normal tissue homeostasis. (molvis.org)
  • Calcified tissue in synovial joints was assessed by micro-computed tomography (micro-CT) and whole-skeleton staining.Results Formation of long bones was found to be normal in KO animals. (bepress.com)
  • Cartilage thickness and proteoglycan staining of articular cartilage in the knee joints of 12-week-old KO mice were increased as compared to controls, with higher cellularity throughout the tissue. (bepress.com)
  • however, they also play important roles in normal tissue so targeting precision is vital. (nanowerk.com)
  • We are interested in whether age-dependent accumulation of senescent cells leads to alterations in tissue microenvironment that is favorable for oncogenesis. (umassmed.edu)
  • WB: Mouse liver tissue lysate. (abcam.com)
  • Obesity elicits immune cell infiltration of adipose tissue provoking chronic low-grade inflammation. (diabetesjournals.org)
  • Regulatory T cells (Tregs) are specifically reduced in adipose tissue of obese animals. (diabetesjournals.org)
  • It is described as a housekeeping enzyme, being responsible for cell-to-cell signaling, tissue homeostasis, and cytoprotection. (medscape.com)
  • Use of human fetal tissue raises several ethical issues, but are there alternative cell sources that can substitute effectively? (lu.se)
  • Through understanding functional recovery in terms of neuronal subtype and connectivity, the work presented in this thesis aims to bring the prospect of CRT closer to the clinic, I also describe the generation of a very promising alternative cell source that could rival fetal tissue. (lu.se)
  • We used histologic, immunofluorescence, RNA sequencing, and metabolic assays to characterize kidneys from these mice and controls during development and up to postnatal day 21. (lww.com)
  • Compared with controls, VHL knockout kidneys are smaller and developmentally delayed by postnatal day 1, and have about half the number of glomeruli at postnatal day 21. (lww.com)
  • The lethality of mdm2 −/− mice before implantation makes it impossible to analyze Mdm2 interaction with p53 in vivo at specific times of development, at postnatal/adult stages, or in specific cell types. (molvis.org)
  • Crypts begin to form around day 7 of postnatal mice (P7), and Paneth cells usually appear within the first 2 weeks. (researchsquare.com)
  • Inhibition of H3K27 trimethylation suppressed crypt formation and Paneth cell maturation on organoids derived from ileum of early second postnatal mouse. (researchsquare.com)
  • Overall, our data show that post-transcriptional modification of histones, particularly H3K27 trimethylation, leads to the structural and functional maturation of Paneth cells during postnatal development. (researchsquare.com)
  • 1997). Within 14 days of postnatal development, Paneth cells mature and express cryptdin proteins as a specific marker (Bry, et al. (researchsquare.com)
  • At the third postnatal week, when PrP expression would normally attain mature levels, PrP0/0 mice showed low performance in the accelerating rotarod and runway tests and the functioning of 40% of granule cells was abnormal. (amrita.edu)
  • In the regenerated uteri, normal hormone responsiveness in early pregnancy was observed, suggesting the regeneration of functional uteri. (jci.org)
  • The morphological and functional maturation of Paneth cells occurred in the first 2 weeks and was accompanied by histone H3 lysine 27 (H3K27) trimethylation. (researchsquare.com)
  • Shane Grealish: Cell Replacement Therapy for Parkinson's Disease: The Importance of Neuronal Subtype, Cell Source and Connectivity for Functional Recovery. (lu.se)
  • The aim of this thesis was to understand how particular factors such as neuronal content, placement and cell source, affect functional outcome after transplantation into the rodent brain. (lu.se)
  • Our results establish a crucial role for E4F during early embryonic cell cycles and reveal an unexpected function for E4F in mitosis. (cnrs.fr)
  • In both human cells in a dish (in vitro) and living mouse brains (in vivo) alpha-synuclein was present in the exact same location as the DNA repair proteins, suggesting alpha-synuclein binds directly to DSBs, and helps repair those breaks. (parkinson.org)
  • A human blood chimeric mouse could serve to harmonize in vitro P. falciparum cultivation and in vivo studies carried out in rodent animal models. (frontiersin.org)
  • In vitro studies based on MCF-7 cell proliferation and induction of vitellogenin in primary culture of rainbow trout hepatocytes. (cdc.gov)
  • 1991. Effects of polychlorinated biphenyls with Ah receptor affinity on lymphoid development in the thymus and the bursa of Fabricius on chick embryos in ovo and in mouse thymus anlagen in vitro . (cdc.gov)
  • This NSG mouse, depleted with γ-chain of the IL-2 receptor, has been shown to better tolerate a variety of human transplanted cells ( 17 - 24 ). (frontiersin.org)
  • post-menopausal women with a higher serum FSH (≥78.3 IU/L) had higher serum TC and LDL-C levels than those with relatively lower FSH levels (40-78.3 IU/L), and ovariectomized mice had higher serum FSH and lipid levels and reduced hepatic LDL receptor expression. (nature.com)
  • Previous studies have shown that cancer cells attract and scavenge HDL by producing high levels of its receptor, SR-B1. (nanowerk.com)
  • 1994. Ah receptor in embryonic mouse palate and effects of TCDD on receptor expression. (cdc.gov)
  • 1999. Adverse reproductive outcomes in the transgenic Ah receptor-deficient mouse. (cdc.gov)
  • Effects of insulin and the glucagon-like peptide 1 receptor agonist liraglutide on the kidney proteome in db/db mice. (lu.se)
  • These data demonstrate clear postmaturational roles for CD28 in FOXP3 + Tregs and provide mechanisms which we believe to be novel to explain how interruption of CD28-ligand interactions may enhance immune responses independent of effects on thymic development or on other cell types. (jci.org)
  • In summary, we demonstrate a role of motile cilia in TGF-β1 sensing and showed that TGF-β1 disturbs TJ permeability of conductive airway epithelia by redistributing CLDN3 from TJs into cell nuclei. (springer.com)
  • The authors used a conditional TET2 knockout model to demonstrate that loss of TET2 in either the HSC or early B-cell stage led to enrichment of GC B cells. (aacrjournals.org)
  • In 1902, French biologist Lucien Cuénot was the first to demonstrate Mendel's theories of inheritance by highlighting the genetics of coat colour characteristics in mice. (yourgenome.org)
  • It is believed that TGF-β1 signalling is involved in controlling epithelial cell proliferation, to drive epithelial-mesenchymal transition (EMT) and it plays a major role in lung fibrosis and emphysema. (springer.com)
  • It is interesting to note that a representative normal prostate epithelial cell line (PrEC) was relatively more resistant to GL-mediated cellular responses compared with prostate cancer cells. (aspetjournals.org)
  • Although a close connection between uterine regeneration and successful pregnancy in both humans and mice has been consistently observed, its molecular basis remains unclear. (jci.org)
  • However, it remains unclear whether the formation of the crypt is related to the maturation of Paneth cells. (researchsquare.com)
  • Introduction: The molecular basis of exocytosis of secretory insulin-containing granules (SGs) during biphasic glucose-stimulated insulin secretion (GSIS) of pancreatic β-cells remains unclear. (endocrine-abstracts.org)
  • We were the first to describe that the hormone-sensitive lipase (HSL) is expressed in beta-cells, controlling break down of triglycerides. (lu.se)
  • Examples of research in which knockout mice have been useful include studying and modeling different kinds of cancer , obesity , heart disease , diabetes , arthritis , substance abuse , anxiety , aging and Parkinson's disease . (wikipedia.org)
  • Insulin-induced β-cell hyperpolarization was sufficient to abolish intracellular calcium concentration ([Ca 2+ ] i ) oscillations measured in pancreatic islets exposed to 10 mmol/l glucose. (diabetesjournals.org)
  • The morphology of dysfunctional Paneth cells is similar to that of a Paneth/goblet intermediate cell. (researchsquare.com)
  • As expected, knockout mice treated with paclitaxel had smaller spleens and thymus glands and underdeveloped bone marrow, compared to normal mice treated with the same drug. (news-medical.net)
  • We study the mechanisms responsible for the tubes becoming cystic using genetically engineered mice that have PKD and cell lines that mimic some of the characteristics of PKD. (nih.gov)
  • This triggered an increase in paracellular permeability via cellular redistribution of claudin 3 (CLDN3) from TJs into cell nuclei followed by disruption of epithelial integrity and formation of epithelial lesions. (springer.com)
  • We have taken a major interest in how mitochondria are genetically regulated, given their pivotal role in cellular energy metabolism and control of insulin secretion from beta-cells. (lu.se)
  • Oxidative stress can denature lipids and proteins [ 10 , 12 - 14 ], as well as induce DNA and RNA fragmentation [ 15 - 17 ], leading to cell dysfunction, injury, and death. (hindawi.com)
  • To search for novel proteins that interact with Galphao, a mouse brain library was screened using the yeast two-hybrid interaction system. (embl-heidelberg.de)
  • Our recent studies as well as others indicate that senescent cells change their secretory patterns of cytokines, chemokines, growth factors, extracellular matrix proteins and proteases. (umassmed.edu)
  • In WT mice, expression of Fos in Hcrt neurons occurs only in the light phase when working for positive reinforcement. (jneurosci.org)
  • It is uniquely expressed in cerebellar Purkinje cells and in retinal bipolar neurons. (embl-heidelberg.de)
  • Pcp2 is expressed in cerebellar Purkinje cells and retinal bipolar neurons, two locations where Galphao is also expressed. (embl-heidelberg.de)
  • This involves transplantation of developing midbrain cells from aborted fetuses, (the part that form mesDA neurons), into the striatum of a PD patient. (lu.se)
  • Paneth cell dysfunction has been reported to correlate with Crohn's disease-like inflammation, showing narrow crypts or loss of crypt architecture in mice. (researchsquare.com)
  • Mitochondrial dysfunction is a common feature of normal aging and is closely associated with the development of age-related neurodegenerative disease [ 1 - 3 ]. (aging-us.com)
  • Hypocretin (Hcrt) cell loss is responsible for narcolepsy, but Hcrt's role in normal behavior is unclear. (jneurosci.org)
  • This has implications both for normal control of insulin release as well as disease processes in islets, also known as lipotoxicity. (lu.se)
  • however, its role in Treg function has been difficult to dissect, as CD28 is required for thymic Treg development, and blockade of CD28-ligand interactions has confounding effects in trans on nonregulatory cells. (jci.org)
  • To investigate the function of CD97 in colorectal carcinogenesis, transgenic Tg(villin-CD97) mice overexpressing CD97 in enterocytes were generated and subjected to azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colitis-associated tumorigenesis. (nih.gov)
  • Further investigation showed that the immune system was involved in the antitumor response in the Rnf5 -/ - mice, with "marked differences in key immune regulatory networks associated with T, DC [dendritic cell], natural killer (NK), and macrophage function. (genengnews.com)
  • The identification of undifferentiated pre-GEPCOT and GEPCOT cells will make it possible to directly study the properties of these cells inside the mouse brain, and to isolate live cells to test how they function. (elifesciences.org)
  • In some cases, normal ovarian function may even return for a period of time. (medscape.com)
  • Thus, ensuring normal mitochondrial function is critical for delaying aging and reducing the risk of age-related neurodegenerative disease [ 4 , 7 , 8 ]. (aging-us.com)
  • I helped create a novel insulin-producing cell line that has become one of the most widely spread tools to understand beta-cell function. (lu.se)
  • We have also described the function of TFB2M, a paralogue of TFB1M, and DIMT1, a TFB1M-homologue, in beta-cells. (lu.se)
  • cell function. (lu.se)
  • Removal of senescent cells, which accumulated with chronological age in parallel to the decline in nerve density, rescued age-induced denervation, reversed Sema3a expression, preserved heart rate patterns, and reduced electrical instability. (bvsalud.org)
  • In Tg murine and normal human colonic enterocytes as well as in colorectal cell lines CD97 was localized preferentially in E-cadherin-based adherens junctions. (nih.gov)
  • Many of these programs generated rich public data sets containing a variety of multi-dimensional molecular and phenotypic data from several organisms including mouse and human. (nih.gov)
  • In the human cell, antioxidant molecules include both nonenzymatic compounds such as glutathione (GSH), thioredoxin (Trx), ascorbate, α -tocopherol, β -carotene, and coenzyme Q10 and enzymes such as catalase, glutathione peroxidase, and superoxide dismutase (SOD) [ 8 ]. (hindawi.com)
  • In fact, DNA damage happens in human cells thousands of times per day. (parkinson.org)
  • They also found that the healthy human cells repaired DSBs more rapidly compared to the knock-out cells, again supporting the role of alpha-synuclein in aiding DNA repair. (parkinson.org)
  • They tested this in two groups of live mice and live human cells: 1. (parkinson.org)
  • Lastly, they tried adding healthy human alpha-synuclein back into the mice without alpha-synuclein to see if it might restore the normal DNA damage response. (parkinson.org)
  • In both healthy human cells and living mouse brains, the laser-induced DSBs, triggered alpha-synuclein to move to the site of DNA damage. (parkinson.org)
  • In diseased human cells and mice carrying the abnormal form of alpha-synuclein, the laser-induced DSBs, impaired alpha-synuclein from moving to the site of DNA damage. (parkinson.org)
  • Removing alpha-synuclein in human cells lead to increased DSB levels after receiving chemotherapy drug (bleomycin) treatment, and a reduction in the ability to repair these DSBs, compared to healthy human cells. (parkinson.org)
  • Controlled reactive professional phagocytic leukocytes in immunodeficient mice allowed for sizeable human blood chimerism and injected huRBCs acted as bona fide host cells for P. falciparum . (frontiersin.org)
  • Therefore, humanized mice capable of harboring the human malaria infection are urgently needed to understand the parasite biology. (frontiersin.org)
  • The reduction in the residual innate immune effectors (mainly cells of monocytes and macrophages lineage) and co-administration of huRBCs supplied with decomplemented human serum through an intravenous route led to the development of a reproducible humanized mouse. (frontiersin.org)
  • Herein we elaborated effects of TGF-β1 on TJs of primary human bronchial epithelial cells. (springer.com)
  • We analyzed mice expressing human p53 transgene (Tg p53 ) selectively in the lens in the presence or absence of Mdm2 . (molvis.org)
  • Clarence Little observed that many mouse tumours acted in the same way as human ones. (yourgenome.org)
  • During his work, Clarence also carried out investigations into cancer and observed that many mouse tumours acted in the same way as human ones. (yourgenome.org)
  • We report an anticancer effect and mechanism of GL against human prostate cancer cells. (aspetjournals.org)
  • Treatment with GL significantly inhibited the viability of human prostate cancer cell line LNCaP (androgen-dependent) and its androgen-independent variant (C81) with an IC 50 of ∼1 μM (24-h treatment), at pharmacologically relevant concentrations standardized to its major active constituent z-guggulsterone. (aspetjournals.org)
  • Enforced expression of HOXB4 dramatically increases the regeneration of murine HSC following transplantation, and enhances the repopulating ability of human SCID repopulating cells. (dissertations.se)
  • To circumvent these obstacles, we have developed two methods for the investigation of human neural cells in culture. (lu.se)
  • The presence of a subclonal population of tumor cells characterized by PDGFRβ expression was further validated in a cohort of human PanNET. (lu.se)
  • In the fifth week of fetal development, neuroblastic cells migrate from the thoracic neural crest to form the sympathetic chains and preaortic ganglia. (medscape.com)
  • RNF5 has also been implicated in the mechanisms that control T-cell priming and immune checkpoint efficiency, so the team investigated whether there was a link between RNF5 knockout on immune checkpoint control and tumor growth. (genengnews.com)
  • Blue cells = expressed in wild-type. (jax.org)
  • However, they were unimpaired relative to wild-type (WT) mice when working for reward during the dark phase or when working to avoid shock in the light or dark phase. (jneurosci.org)
  • Unexpectedly, we found a CD97 cDNA copy number-dependent reduction of DSS-induced colitis in Tg compared to wild-type (WT) mice that was confirmed by applying a simple DSS protocol. (nih.gov)
  • 2009). However, the relation between the localization of Paneth cells at the bottom of the crypt and their maturation remains to be elucidated. (researchsquare.com)
  • In 1994, through application of broad range molecular cell signal transduction and possibly eukaryotic transcrip- amplification and DNA sequencing, the causative agent tion. (cdc.gov)
  • At Berkeley Lab, Yaswen engineered normal breast cells, donated by patients who had undergone breast-reduction surgery, to carry a molecular construct that caused the cells to express MYC only when a particular chemical compound was applied. (ucsf.edu)
  • Our findings identify a novel role for VHL in mediating nephron progenitor differentiation through metabolic regulation, and suggest that VHL is required for normal kidney development. (lww.com)
  • This was made possible by a metabolomics approach, using NMR to map metabolic pathway activity in cells. (lu.se)
  • I'd like to stress that we did this work in a mouse model,' Hopper-Borge says. (news-medical.net)
  • Consistently, the results indicate that FSH, independent of estrogen, increases the serum cholesterol level in this mouse model. (nature.com)
  • This makes the mouse an extremely useful model organism. (yourgenome.org)
  • We here established a mouse model of decellularized uterine matrix (DUM) transplantation. (jci.org)
  • Experimental procedures of a mouse DMT model. (jci.org)
  • A ) A schematic illustration of a mouse model of decellularized matrix transplantation (DMT). (jci.org)
  • In paper №1, I detail the neurodegenerative and behavioural outcomes in a mouse lesion model of PD, which can be used as a platform for the development of novel therapeutic strategies. (lu.se)
  • The results provide the first evidence from living organisms that Abcc10 is a cell's built-in protection against the effects of powerful drugs, and raises the possibility of using Abcc10 inhibitors to break down that resistance and sensitize tumor cells to anticancer agents. (news-medical.net)
  • For that reason, Hopper-Borge thinks the best approach may be developing inhibitors that work only in tumor cells or coming up with compounds that modulate, rather than completely inhibit the protein's activity. (news-medical.net)
  • As a result, there is an emergent need to explore previously unmapped mechanisms regulating distinct subpopulations of tumor cells and to understand their contribution to tumor progression and treatment response. (lu.se)
  • Mouse cone photoreceptors express two distinct visual arrestins: Arr1 and Arr4. (nih.gov)
  • A paper published electronically this week by Nature Genetics offers important new insights into the development and differentiation of rod and cone photoreceptors, the light-sensitive cells in the eye's retina that initiate vision and are essential for clear sight. (sciencedaily.com)
  • Collectively, our data suggest that huRBCs reconstituted NSG mice infected with attenuated P . falciparum is a valuable tool to explore the role of C9 mutation in the growth and survival of parasite mutants and their response to the host's immune responses. (frontiersin.org)
  • However, an acute effect of insulin in modulating β-cell electrical activity and its underlying ionic currents has not been reported. (diabetesjournals.org)
  • Using the perforated patch clamp technique, we found that insulin (1-600 nmol/l) but not IGF-1 (100 nmol/l) reversibly hyperpolarized single mouse β-cells and inhibited their electrical activity. (diabetesjournals.org)
  • The effects of insulin were reversed by tolbutamide, which decreased cell conductance to 0.5 ± 0.1 nS and shifted the current reversal potential to −25.2 ± 2.3 mV. (diabetesjournals.org)
  • In cell-attached patches, single ATP-sensitive K + (K ATP ) channels were activated by bath-applied insulin and subsequently inhibited by wortmannin. (diabetesjournals.org)
  • My scientific work has focused on the insulin-secreting beta-cells in the islets of Langerhans. (lu.se)
  • We examined regulation of lipid partioning in beta-cells and its control of insulin secretion. (lu.se)
  • Most importantly, we described the critical role of pyruvate cycling in insulin secretion and how it underlies stimulus-secretion coupling in the beta-cell. (lu.se)