• This review focuses on recent findings using genetically modified mice (gene knockouts and transgenic 'green acrosome' mice) to study the effects of eliminating acrosomal matrix-associated proteins on sperm structure and function. (nih.gov)
  • Some gene knockouts produce infertile phenotypes with obviously missing, specific activities that affect acrosome biogenesis during spermatogenesis or interfere with acrosome function in mature sperm. (nih.gov)
  • 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)
  • Gene knockout in rats is much harder and has only been possible since 2003. (wikipedia.org)
  • They are important animal models for studying the role of genes which have been sequenced but whose functions have not been determined. (wikipedia.org)
  • Humans share many genes with mice. (wikipedia.org)
  • Knockout mice also offer a biological and scientific context in which drugs and other therapies can be developed and tested. (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)
  • 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)
  • 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 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)
  • [3] Many mouse models are named after the gene that has been inactivated. (wikipedia.org)
  • Other mouse models are named according to their physical characteristics or behaviours. (wikipedia.org)
  • The use of genetically engineered mouse models has yielded new mechanistic information that complements recent, important in vivo imaging studies. (nih.gov)
  • White heterozygous mice can subsequently be crossed to produce mice that are homozygous for the knocked out gene. (wikipedia.org)
  • They are widely used in knockout experiments, especially those investigating genetic questions that relate to human physiology . (wikipedia.org)
  • Methods: Total RNA was isolated from PNN knockdown human corneal epithelial (HCET) cells or Pnn-deficient mouse corneas, and subjected to real-time-PCR (RT-PCR) assays, and the alternatively spliced lncRNAs were counted. (molvis.org)
  • 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)
  • To test this idea, first author Jacqueline Burré and colleagues immunoprecipitated SNARE complexes from the brains of wild-type mice, CSPα knockout mice, and from CSPα knockouts rescued by transgenic α-synuclein. (alzforum.org)
  • Conversely, MPTP-mediated neuronal death disappeared in transgenic mice that overexpressed Nrf2-even when expression of the gene was restricted to astrocytes (by putting into Nrf2 knockout mice a Nrf2 transgene driven by an astrocyte-specific promoter). (alzforum.org)
  • The contributors describe strategies for producing genetic models, including transgenic germline models, gene knockouts and knockins, and conditional and inducible systems, as well as models derived using transposon-based insertional mutagenesis, RNA interference, viral-mediated gene delivery, and chemical carcinogens. (cshlpress.com)
  • Mouse knockout technology provides a powerful means of elucidating gene function in vivo , and a publicly available genome-wide collection of mouse knockouts would be significantly enabling for biomedical discovery. (nature.com)
  • Now that the human and mouse genome sequences are known 1 , 2 , 3 , attention has turned to elucidating gene function and identifying gene products that might have therapeutic value. (nature.com)
  • The large-scale production and analysis of induced genetic mutations in worms, flies, zebrafish and mice have greatly accelerated the understanding of gene function in these organisms. (nature.com)
  • Current technology also permits insertion of 'reporter' genes into the knocked-out gene, which can then be used to determine the temporal and spatial expression pattern of the knocked-out gene in mouse tissues. (nature.com)
  • The RFA calls for two approaches: a) to generate (preferably in C57BL/6) null mutations for the mouse genes for which there has not yet been a null mutation produced and/or b) to produce a nearly complete set of mouse null mutations in C57BL/6 ES cells or mice by transposon or gene trapping mutagenesis. (nih.gov)
  • In contrast, mice deficient for the inducible nitric oxide synthase gene ( NOS2 −/−) did not show any cognitive changes when challenged with LPS. (jneurosci.org)
  • Toward this end, they engineered mice that expressed a reporter gene (human placental alkaline phosphatase) under the control of the ARE promoter. (alzforum.org)
  • But how could this rescue CSPα knockout mice from massive neuronal death? (alzforum.org)
  • It is time to harness new technologies and efficiencies of production to mount a high-throughput international effort to produce and phenotype knockouts for all mouse genes, and place these resources into the public domain. (nature.com)
  • Furthermore, lack of RelA leads to embryonic lethality and liver degeneration in knockout mice, whereas mice lacking p50 or RelB are immunodeficient but otherwise develop normally to adulthood. (jci.org)
  • This FOA issued by the Office of Strategic Coordination, Office of the Director, National Institutes of Health, solicits grant applications from institutions/ organizations that propose to develop and implement a Data Coordination Center and Database (DCCDB) as part of the Knockout Mouse Phenotyping Project (KOMP 2 ). (nih.gov)
  • The purpose of this RFA is to solicit applications for a project to develop and implement a Data Coordination Center (DCC) as part of the Knockout Mouse Project (KOMP) research network. (nih.gov)
  • The KOMP research network is composed of four components: 1) one or more projects called for in RFA-HG-05-007 , whose goal is to make maximum progress towards completing the set of mouse knockouts across the entire mouse genome in the most widely use mouse strain, C57BL/6. (nih.gov)
  • The DCC will be funded primarily to develop, house, and maintain databases to track the progress of the pipelines for producing the knockout mutations, and to deliver this information to the members of the KOMP research network, NIH staff, and the public. (nih.gov)
  • Electrophysiological readouts in brain slices of wild-type and CSFα knockout mice remained constant regardless of whether or not the animals had an α-synuclein transgene. (alzforum.org)
  • C57BL/6 and NOS2 knock outs were crossed resulting in NOS2 heterozygous mice. (jneurosci.org)
  • These mice were subsequentially crossed resulting in C57BL/6 wild-type and homozygous NOS2 knock-out mice, which were then used for the study. (jneurosci.org)
  • Further the test clearly dissected response from place strategies, which were both successfully acquired by C57Bl/6N mice. (uni-marburg.de)
  • Appreciation of the power of mouse genetics to inform the study of mammalian physiology and disease, coupled with the advent of the mouse genome sequence and the ease of producing mutated alleles, has catalyzed public and private sector initiatives to produce mouse mutants on a large scale, with the goal of eventually knocking out a substantial portion of the mouse genome 12 , 13 . (nature.com)
  • Given that the vast majority of the human genome is transcribed, the mouse models developed by Sauvageau et al. (elifesciences.org)
  • have developed several lines of knockout mice to investigate a subset of noncoding RNA molecules known as long intergenic noncoding RNAs (lincRNAs). (elifesciences.org)
  • Several months ago, Johnson and colleagues reported that targeting Nrf2 overexpression to astrocytes delayed motor neuron degeneration in a mouse model of amyotrophic lateral sclerosis (see ARF related news story ). (alzforum.org)
  • and 3) one or more repositories to collect existing mouse knockouts (repatriation) and for storage and distribution of the materials from the first two RFAs described and 4) the DCC. (nih.gov)
  • The laboratory mouse. (uni-marburg.de)
  • The laboratory mouse as a model organism provides many advantages to study the underlying mechanisms as one can directly interfere with brain functions via a number of tools including genetic manipulation. (uni-marburg.de)
  • The laboratory mouse is an important model for addressing questions in cancer biology. (cshlpress.com)
  • To investigate the functional relevance of lncRNAs in various physiological conditions, we have developed a collection of 18 lncRNA knockout strains in which the locus is maintained transcriptionally active. (elifesciences.org)
  • Expression analysis demonstrated distinct changes in the content of synaptic proteins in wild-type mice, which were not observed in the NOS2 −/− mice. (jneurosci.org)
  • Studies in knockout mice have shown distinct functions for different members of the NF-κB/Rel family. (jci.org)
  • Many studies are uncovering functional roles for long noncoding RNAs (lncRNAs), yet few have been tested for in vivo relevance through genetic ablation in animal models. (elifesciences.org)
  • The Effects of Genetic Background of Mouse Models of Cancer: Friend or Foe? (cshlpress.com)
  • However, ithas never been shown that LTCCs directly regulate the MEMRI contrast in vivo, which would be essential to establish it as a functional tool in order to measure brain activity in the living mouse brain. (uni-marburg.de)
  • Second, I investigated the contribution of Cav1.2 and Cav1.3 on MEMRI contrast with the help of corresponding knockout mice. (uni-marburg.de)
  • Expression analysis showed that LPS-treated NOS2 −/− mice had lower brain mRNA levels for proinflammatory factors compared with wild-type mice. (jneurosci.org)
  • Moreover, the authors found that restoring expression of α-synuclein in cultured neurons from the triple knockout mice helped re-establish SNARE complexes, and did so in a dose-dependent way. (alzforum.org)
  • Two months after LPS treatment, wild-type mice committed more working and reference memory errors than controls. (jneurosci.org)
  • Immunohistochemical analysis demonstrated that LPS did not lead to neuronal cell death but caused sustained microglial activation in wild-type as compared to NOS2 −/− mice. (jneurosci.org)
  • Nrf2 knockout mice showed increased sensitivity to the toxin, compared with wild-type animals. (alzforum.org)
  • Given that the CSPα knockout mice had trouble assembling SNARE complexes, the researchers figured α-synuclein might compensate for its absence by helping SNARE proteins work properly. (alzforum.org)
  • Ongoing studies in the AD mice should help tease out these possibilities, Wilcock noted. (alzforum.org)
  • An appendix specifically addresses the use of mouse cancer models in translational studies and the integration of mouse and human clinical investigations. (cshlpress.com)
  • In this study, we used a murine sepsis model to demonstrate that bacterial lipopolysaccharide (LPS) causes long-term cognitive deficits in mice. (jneurosci.org)
  • To better understand the underlying principles of memory processes, efforts still have to rely on animal research. (uni-marburg.de)
  • However, these investigations are likely to reflect the immediate effects of SE on brain functions, since the experimental paradigms applied were of rather acute nature, exposing animals or brain slices to LPS directly or just hours before the respective analysis. (jneurosci.org)
  • These experiments reveal that lincRNAs have a strong influence on the overall viability of mice, and also on a number of developmental processes, including the development of lungs and the cerebral cortex. (elifesciences.org)
  • I had been able to demonstrate that theWCMwas particularly suitable for mice because it prevented most unwanted strategies that mice often adopt during the Morris water maze task. (uni-marburg.de)
  • As they aged, these mice made SNARE complexes less robustly, and had lower levels of synaptobrevin-2, relative to young animals. (alzforum.org)
  • Correlating with vascular Aβ load, the AD mice also showed decreased levels of an anchoring protein (dystrophin 1) common to these channels. (alzforum.org)
  • Accordingly, HPC-lesioned mice were unable to acquire a place strategy, however, they adopted a response strategy instead. (uni-marburg.de)
  • In this week's PNAS Early Edition, a Johnson-led team shows that a similar strategy works in the MPTP mouse model for Parkinson disease. (alzforum.org)
  • However, mice failed to relearn under response training independent of the original navigation strategy that was adopted within the week before. (uni-marburg.de)