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In 2007, the International Knockout Mouse Consortium (IKMC) made the ambitious promise to generate mutations in virtually every protein-coding gene of the mouse genome in a concerted worldwide action. Now, 5 years later, the IKMC members have developed high-throughput gene trapping and, in particular, gene-targeting pipelines and generated more than 17,400 mutant murine embryonic stem (ES) cell clones and more than 1,700 mutant mouse strains, most of them conditional. A common IKMC web portal (www.knockoutmouse.org) has been established, allowing easy access to this unparalleled biological resource. The IKMC materials considerably enhance functional gene annotation of the mammalian genome and will have a major impact on future biomedical research.
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Functional Annotation of the Mouse Genome, it will complete the International Knockout Mouse Consortium (IKMC) resource of mutations for all protein coding genes. Furthermore, it will maximize the utility of the conditional IKMC resource by generating up to 250 different, mostly inducible Cre driver mouse lines. In addition, EUCOMMTOOLS will develop novel tools to enhance the versatility of the IKMC resource. EUCOMMTOOLS vectors, mutant ES cells and mutant mice are distributed worldwide: EUCOMMTOOLS mutant ES cells and vectors can be obtained from the European Mouse Mutant Cell Repository (EuMMCR). EUCOMMTOOLS mutant mice are archived and distributed by the European Mouse Mutant Archive (EMMA). Knockout-first Mutant Alleles: EUCOMMTOOLS will create 3500 C57Bl/6 conditional mutant alleles for single-exon (or otherwise previously conditionally untargeted) protein-coding mouse genes. These alleles will be made predominantly by introducing an "artificial intron", containing a standard EUCOMM promoter-driven targeting cassette, into the coding sequence of the single-exon gene. Cre Resources: EUCOMMTOOLS will engineer 500 new Cre C57Bl/6 ES cell lines by Cre knock-ins into genes with useful expression patterns. The resource will be made with inducible forms of Cre recombinase such as CreERT2. Up to 250 lines of Cre driver mice on a pure C57Bl/6N background will be generated and the Cre expression patterns documented and annotated in day P14 and P56. These mice will form a matched Cre driver resource for C57Bl/6N mice produced from conditional IKMC resources. Research, Technology and Complementary Reagents: EUCOMMTOOLS will develop novel technologies to add value, depth and flexibility to existing IKMC ES cell and mouse resources. Key areas include: * Development of novel recombinase based regulatory switches * Exploration of zinc-finger nuclease stimulated homologous recombination strategies in fertilized oocytes * Development and validation of complementary modular vector reagents which enable the construction of new useful knock-in alleles such as fluorescent and other reporters, site specific recombinases, and mutant cDNAs. These novel alleles can be constructed either by re-utilizing existing IKMC modular vector resources or directly modifying existing targeted IKMC ES cell lines by RMCE.
View all literature mentionsEmbryonic stem cell distribution unit that distributes material arising within European Conditional Mouse Mutagenesis Program consortium, currently targeting vectors and ES cells. Upon user request EUCOMM grow targeting vectors from glycerol stocks and prepare vector DNA. Identity of vector is verified by restriction mapping. Upon user request EUCOMM thaw, expand and re-freeze several aliquots of desired ES cell clone. Standard controls include PCR based assay. Upon additional request EuMMCR unit develops genotyping PCR, which can be used to genotype chimeric mice that may be generated using those ES cell clones.
View all literature mentionsResource for any researcher looking to obtain knockout mice and embryonic stem (ES) cells quickly and with favorable intellectual property (IP) terms. Our resources include the world’s largest gene trap library of ES cells in the C57BL/6N mouse strain and a constantly expanding repository of cryopreserved germplasm of knockout lines. TIGM provides both ES cell clones and mice as well as other transgenic core services including CRISPR/Cas9-based genome modifications within the Texas A&M system and to the public and private international research community.
View all literature mentionsCre expressing mice under the control of promoters with a design focus on the brain. Each promoter is derived from human sequence, but the resulting expression is assessed in the mouse for the activation of a LacZ reporter gene by the Cre activity. Promoters tested as large MaxiPromoters (BACs inserted into the mouse genome) and MiniPromoters (plasmid-based sequences inserted either into the mouse genome or introduced within AAV viruses). The Cre-related project continues from the Pleiades Promoter Project. Here is the list of genes for which icre/ERT2 mice are currently in development: AGTR1, CARTPT, CLDN5, CLVS2, CRH, GABRA6, HTR1A, HTR1B, KCNA4, KDM5C, MKI67, NEUROD6, NKX6-1, NOV, NPY2R, NR2E1, OLIG2, POU4F2, SLITRK6, SOX1, SOX3, SOX9,, SPRY1, VSX2
View all literature mentionsAn independent, nonprofit organization focused on mammalian genetics research to advance human health. Their mission is to discover the genetic basis for preventing, treating, and curing human disease, and to enable research for the global biomedical community. Jackson Laboratory breeds and manages colonies of mice as resources for other research institutions and laboratories, along with providing software and techniques. Jackson Lab also conducts genetic research and provides educational material for various educational levels.
View all literature mentionsDatabase of the international consortium working together to mutate all protein-coding genes in the mouse using a combination of gene trapping and gene targeting in C57BL/6 mouse embryonic stem (ES) cells. Detailed information on targeted genes is available. The IKMC includes the following programs: * Knockout Mouse Project (KOMP) (USA) ** CSD, a collaborative team at the Children''''s Hospital Oakland Research Institute (CHORI), the Wellcome Trust Sanger Institute and the University of California at Davis School of Veterinary Medicine , led by Pieter deJong, Ph.D., CHORI, along with K. C. Kent Lloyd, D.V.M., Ph.D., UC Davis; and Allan Bradley, Ph.D. FRS, and William Skarnes, Ph.D., at the Wellcome Trust Sanger Institute. ** Regeneron, a team at the VelociGene division of Regeneron Pharmaceuticals, Inc., led by David Valenzuela, Ph.D. and George D. Yancopoulos, M.D., Ph.D. * European Conditional Mouse Mutagenesis Program (EUCOMM) (Europe) * North American Conditional Mouse Mutagenesis Project (NorCOMM) (Canada) * Texas A&M Institute for Genomic Medicine (TIGM) (USA) Products (vectors, mice, ES cell lines) may be ordered from the above programs.
View all literature mentionsThe CREATE consortium represents a core of major European and international mouse database holders and research groups involved in conditional mutagenesis, primarily to develop a strategy for the integration and dissemination of Cre driver strains for modelling aspects of complex human diseases in the mouse. Collectively the participants have amassed a significant number of these strains in their respective databases. Therefore one of the goals of CREATE is to provide a unified portal for worldwide access to these critical resources. The portal can either be searched through an advanced BioMart interface, by driver name, or by anatomical site of expression using Embryonic Mouse Anatomy Project (EMAP) and Mouse Anatomy (MA) ontology terms. Search results link back to the original source of the data for more detailed information and to IMSR to order mice if available. The ontology browser is particularly useful as it enables the CREATE consortium to identify cell and tissues that are not currently covered by existing lines. CREATE also aims to coordinate the production of suitable lines by the Cre generation projects described above. Through the CREATE portal, the CREATE consortium aims to develop a strategy for the production, integration and dissemination of new Cre driver strains for modelling aspects of complex human diseases in the mouse. CREATE is also developing a roadmap for harnessing emerging technologies and methods for improving Cre-mediated recombination in vivo through targeted, intensive workshops and discussion forums on the portal. This will entail review of construct design options for classical transgenic constructs (promoter/enhancer used, small size <2025 Kb) vs large transgenic constructs (BAC, P1, YAC etc.); methods used for Cre transgenic lines including random vs targeted integration, position independent expression loci, or replacement of endogenous coding sequences with Cre recombinase under the control of the endogenous locus. CREATE provides a platform for discussion of additional issues specific to inducible Cre strategies including background activity before induction, inducibility (kinetics), efficiency, and protocols used for induction of Cre recombinase activity. Additional components of the technology roadmap will be the cataloguing of other existing methodologies (rtTA, FLP, Dre) of mouse genome modification, sharing information on validated Cre mutant lines as well as identification and assessment of new methods of mutagenesis such as RNAi and other emerging technologies. Other discussion topics addressed through surveys on the CREATE portal include the characterization of Cre lines (specificity of expression/deletion; efficiency of expression/ deletion; reproducibility of deletion from animal to animal for the same floxed allele; reproducibility with different floxed alleles; timing of expression/deletion, etc.), the extent to which Cre expression changes upon backcrossing to specific genetic backgrounds through variegation and silencing; potential phenotypes caused by either integration- mediated mutagenesis or Cre ''toxicity''; and other factors affecting the specificity of Cre-mediated expression/deletion. CREATE regularly integrates common fields from the Cre-X, CreZOO and the MGI recombinase portal resources described below. The data in common consists of: * Transgene or Knock-in name. * MGI ID of allele. * Driver. * Anatomical site of expression. * Pubmed ID. * IMSR strain name and link. * Inducibility (YES/NO).
View all literature mentionsCentral repository for the physical archive and distribution of cryopreserved ES cells, spermatozoa, ova, embryos, and non-germ cell tissue DNA generated by Canada''''s mouse genome effort. The CMMR acts in coordination with other repositories worldwide and is establishing a nation-wide network of repository nodes to house sub-sets of the resources generated across Canada. The CMMR is the repository and distribution center for the North American Conditional Mouse Mutagenesis project (NorCOMM). The CMMR also collects and stores somatic tissue from mouse models in a variety of formats (fixed, embedded, and glass-slide mounted) enabling world wide access to specimens from established mouse models. Services include: * Embryo cryopreservation and recovery * Ovary cryopreservation and recovery * Ovary transplant * Sperm cryopreservation and recovery * Strain services, including rederivation by IVF, speed expansion and strain rescue * NorCOMM ES cell withdrawal * Non-NorCOMM ES cell expansion
View all literature mentionsCenter that produces knockout mice and carries out high-throughput phenotyping of each line in order to determine function of every gene in mouse genome. These mice will be preserved in repositories and made available to scientific community representing valuable resource for basic scientific research as well as generating new models for human diseases.
View all literature mentionsDatabase of mouse research resources at Sanger: BACs, targeting vectors, targeted ES cells, mutant mouse lines, and phenotypic data generated from the Institute''''s primary screen. The Wellcome Trust Sanger Institute generates, characterizes, and uses a variety of reagents for mouse genetics research. It also aims to facilitate the distribution of these resources to the external scientific community. Here, you will find unified access to the different resources available from the Institute or its collaborators. The resources include: 129S7 and C57BL6/J bacterial artificial chromosomes (BACs), MICER gene targeting vectors, knock-out first conditional-ready gene targeting vectors, embryonic stem (ES) cells with gene targeted mutations or with retroviral gene trap insertions, mutant mouse lines, and phenotypic data generated from the Institute''''s primary screen.
View all literature mentionsCurated data about all recombinase-containing transgenes and knock-ins developed in mice providing a comprehensive resource delineating known activity patterns and allows users to find relevant mouse resources for their studies.
View all literature mentionsRepository of mouse vectors, ES cells, mice, embryos, and sperm generated by NIH KOMP Mutagenesis Project. In addition, KOMP Repository offers services in support of KOMP products, including ES cell microinjection, vector cloning, post-insertional modification of cloned ES cells, cryopreservation, assisted reproduction techniques (IVF, ICSI) and mouse breeding, pathology services, phenotyping services, etc. KOMP Repository is final component of more than $50 million trans-NIH initiative to increase availability of genetically altered mice and related materials. The University of California, Davis (UC Davis) and Children''s Hospital Oakland Research Institute (CHORI) in Oakland, Calif., are collaborating to preserve, protect, and make available about 8,500 types of knockout mice and related products available to research community. Products are generated by two KOMP mutagenesis teams (CSD consortium and Regeneron Inc). All KOMP products generated by CSD consortium and Regeneron are available through KOMP Repository. Notice as of December 19, 2019: Materials from KOMP Repository have been deposited into MMRRC, including all mouse models and mouse embryonic stem cell lines. Eventually www.komp.org will be sunsetting, and IMSR will remove KOMP Repository listings, since they were double listed in MMRRC. MMRRC will contain the most accurate and up to date resource models.
View all literature mentionsCommunity model organism database for laboratory mouse and authoritative source for phenotype and functional annotations of mouse genes. MGD includes complete catalog of mouse genes and genome features with integrated access to genetic, genomic and phenotypic information, all serving to further the use of the mouse as a model system for studying human biology and disease. MGD is a major component of the Mouse Genome Informatics.Contains standardized descriptions of mouse phenotypes, associations between mouse models and human genetic diseases, extensive integration of DNA and protein sequence data, normalized representation of genome and genome variant information. Data are obtained and integrated via manual curation of the biomedical literature, direct contributions from individual investigators and downloads from major informatics resource centers. MGD collaborates with the bioinformatics community on the development and use of biomedical ontologies such as the Gene Ontology (GO) and the Mammalian Phenotype (MP) Ontology.
View all literature mentionsNon-profit repository for the collection, archiving (via cryopreservation) and distribution of relevant mutant strains essential for basic biomedical research. Users may browse by strain, gene, phenotype, or human disease. Its primary objective is to establish and manage a unified repository for maintaining medically relevant mouse mutants and making them available to the scientific community. Therefore, EMMA archives mutant strains and distributes them to requesting researchers. EMMA also hosts courses in cryopreservation, to promote the use and dissemination of frozen embryos and spermatozoa. Dissemination of knowledge is further fostered by a dedicated resource database. Anybody who wants their mutant mouse strains cryopreserved may deposit strains with EMMA. However depositors must be aware that these strains become freely available to other researchers after being deposited.With more than 8400 mutant mouse strains and asmall but increasing number of rat mutant strains available, EMMA is the primary mouse repository in Europe and the third largest non-profit repository worldwide.
View all literature mentionsCenter that imports, archives, maintains, and distributes mutant mouse alleles as live mice, frozen germplasm, stem cells, and molecular vectors for use in biomedical research. The MMRRC Davis receives transgenics, knockouts, and other kinds of mutant mouse lines at no cost to the donor, and after re-derivation and cryopreservation, distributes breeding stock, germplasm, cells, or tissues of genetically-defined and pathogen-free mice for a small fee to requesting investigators.
View all literature mentionsNational public repository system for mutant mice. Archives and distributes scientifically valuable spontaneous and induced mutant mouse strains and ES cell lines for use by biomedical research community. Includes breeding/distribution facilities and information coordinating center. Mice strains are cryopreserved, unless live colony must be established. Live mice are supplied from production colony, from colony recovered from cryopreservation, or via micro-injection of cell line into host blastocysts. MMRRC member facilities also develop technologies to improve handling of mutant mice, including advances in assisted reproductive techniques, cryobiology, genetic analysis, phenotyping and infectious disease diagnostics.
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