MMRRC Major Collections

Background

No Data

MMRRC Holdings

The MMRRC holds over 342 mutant strains in this collection and the number continues to grow. View MMRRC catalog of all BaSH EUCOMM lines.

Distribution

Strains are distributed using the BaSH EUCOMM Conditions of Use* (COU), and are available only to investigators at nonprofit institutions.

* The preceding link is to the COU text only; the COU web form will be provided via email after an order has been placed. The email should be forwarded to the institutional official for completion.

Note: Some BaSH EUCOMM strains were submitted as sperm. These strains were not cryopreserved by the MMRRC, and we have not assessed the quality of this material. We have extensive experience with recovery of mice from cryopreserved sperm of varying quality using techniques such as IVF and ICSI and are confident that we will have success in most if not all cases. However, because of the unknown quality of these sperm samples, we will restrict recovery efforts to two attempts for each order.Subsequent attempts can be performed for additional charges.

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Background

The majority (but not all) of the BayGenomics ES cell lines were generated from 129P2/OlaHsd (formerly 129/Ola) ES cell lines, predominantly the E14Tg2A.4 parental subclone.

MMRRC Holdings

The MMRRC holds over 14,000 lines in this collection. View MMRRC catalog of all BayGenomics lines. The vast majority of BayGenomics cell lines have been correctly identified, as judged by DNA sequencing (i.e., repeat determination of the DNA sequence tag when the ES cell clone is requested). However, incorrectly identified ES cell clones are occasionally encountered, either because of human error or because a thawed ES cell line gets overgrown by a contaminating ES cell line. Therefore, we strongly recommend that you request verification of the identity of your ES cell line by DNA sequencing. There is an additional fee for DNA sequence verification of your clone (see below), but that fee is well worth it in terms of your overall investment in a gene knockout project. To reconfirm the identity of your ES cell line by DNA sequencing, simply indicate that on your on-line application.

We also recommend that recipients of ES cells re-verify the identity of the ES cell line by RT-PCR and/or Southern blot analysis (Genotyping BayGenomics Mice).

Most, but not all BayGenomics ES cell lines yield germline-transmitting chimeras. If more than one ES cell line is available for your "gene-of-interest", we recommend that you order several of the ES cell lines. Ordering more than one ES cell line for a specific "gene-of-interest" will increase the chances of success.

Distribution

Clones are available only to investigators at non-profit institutions for non-commercial, academic research purposes only. They are distributed using the MMRRC Conditions of Use (COU). Note: The preceding link is to the COU text only; the COU user form will be provided after order submission. To inquire about obtaining these cell lines, please contact MMRRC Customer Service at service@mmrrc.org or (207) 288-6009 (international) or (800) 910-2291 (North America). The MMRRC can further assist you by deriving embryos and/or live mice from these cells and providing services such as: genetic screening, multi-tier phenotyping, barrier housing and colony management.

For additional assistance about these clones, please contact the MMRRC at UC Davis at (530) 754-3290 between 9AM and 4PM PST or email mmrrc@ucdavis.edu.

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Background

The Beta Cell Biology Consortium (BCBC) is a team science initiative that was established by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) in 2001. Currently, the BCBC consists of 29 extramural scientists and scientists from two intramural NIDDK laboratories.

MMRRC Holdings

The MMRRC holds over 15 strains in this collection. View MMRRC catalog of all BCBC lines.

Distribution

Strains are distributed using the MMRRC Conditions of Use *(COU). Some, but not all, BCBC strains are restricted to investigators at non-profit institutions.

* The preceding link is to the COU text only; the COU user form will be provided after order submission.

Citations

Information excerpted from the BCBC website; additional information can be found there.

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Background

Beutler Strains are from the MUTAGENETIX archive of phenotypes and mutations produced in Dr. Bruce Beutler’s Lab (Center for the Genetics of Host Defense, The University of Texas Southwestern Medical Center). The Beutler strains have been produced by random N-ethyl-N-nitrosourea (ENU)-induced germline mutagenesis.

In the Beutler lab, male C57BL/6J mice, termed first generation (G1) mice, are mutagenized with ENU and their exomes sequenced. The G1 mice are subsequently propagated to the second (G2) and third generations (G3), whereby ENU-induced mutations will be homozygous reference (wild-type), heterozygous, or homozygous variant. The G3 mice are actively screened for immunological phenotypes. However, many non-immunological phenotypes (e.g. changes in pigmentation, metabolism, behavior, development morphology, or lethality) are often incidentally identified, and some of them address major biological questions. Mutations are positionally cloned more rapidly than they can be investigated in depth, and in many cases, more rapidly than they can be published in conventional journals. Therefore, all mutations in each G1 mouse are described on the MUTAGENETIX website, as are the essential phenotypic characteristics, when available.

All information on chromosomal locations and critical region intervals are currently based on Ensembl Mouse annotation (release 71). Specific sequence information (gene sequences, positions of mutations, etc.) is based on the NCBI GRCm38 (mm10) mouse assembly. Individual strain records on the MUTAGENETIX website contain links to specific cDNA sequences and/or genomic DNA sequences in the NCBI database.

MMRRC Holdings

The MMRRC holds over 3550 mutant strains in this collection and the number continues to grow. View MMRRC catalog of all Beutler Mutagenetix lines.

Distribution

Strains are distributed using the MMRRC Conditions of Use *(COU). Mice are available only to investigators at non-profit institutions.

* The preceding link is to the COU text only; the COU web form will be provided via email after order submission. The email should be forwarded to your institutional official for completion.

Some Beutler strains were submitted as a sperm collection, and because these strains were not cryopreserved by the MMRRC, we have not assessed the quality of this material. We have extensive experience with recovery of mice from cryopreserved sperm of varying quality using techniques such as IVF and ICSI and are confident that we will have success in most if not all cases. However, because of the unknown quality of these sperm samples, we will restrict recovery efforts to two attempts for each order. Subsequent attempts can be performed for additional charges.

Citations

Information excerpted from the MUTAGENETIX website; additional information can be found there.

MUTAGENETIX should be cited in journal articles or on-line publications using the following conventions: {Authors, Science Writers, Beutler B}. Record for {allele name}, updated {date of last update}. MUTAGENETIX (TM), B. Beutler and colleagues, Center for the Genetics of Host Defense, UT Southwestern, Dallas, TX. Accessed {date of download}. World Wide Web URL: http://mutagenetix.utsouthwestern.edu.

Citations should also acknowledge that these mice were received from the MMRRC, and mention RRID:MMRRC:0XXXX, where 0XXXX is replaced by the MMRRC ID number.

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Background

The Comparative Mouse Genomics Centers Consortium (CMGCC) was initiated by the National Institute of Environmental Health Sciences’ (NIEHS) Environmental Genome Project to develop transgenic and knockout mouse models based on human DNA sequence variants in environmentally responsive genes. These mouse models are useful tools to improve our understanding of the biological significance and functional relevance of these polymorphisms in human disease, particularly when validated with controlled exposures and environmental challenges. This program has resulted in the discovery of unique variants in environmentally responsive genes, the development of a number of resources, and capacity building in the environmental epidemiology communities in order to incorporate gene-environment hypotheses and tools into human population-based studies on a number of environmentally relevant diseases. This Consortium requires extensive collaboration and multidisciplinary research in molecular biology, biochemistry, structural biology, as well as expertise in mouse genetics and pathology, to achieve the following goals:

  • Identify relevant and feasible mouse models for development by the Consortium;
  • Identify mouse models that are relevant to human environmental health; and
  • Validate developed mouse models that are relevant to environmentally induced human diseases.
MMRRC Holdings

The models developed by the Consortium are being made available to the scientific community through an arrangement with the National Center for Research Resources (NCRR). The MMRRC holds over 20 transgenic and knockout strains in this collection. View MMRRC catalog of all CMGCC lines.

Distribution

Strains are distributed using the MMRRC Conditions of Use *(COU). Some, but not all, CMGCC strains are restricted to investigators at non-profit institutions.

* The preceding link is to the COU text only; the COU web form will be provided via email after an order has been placed. The email should be forwarded to the institutional official for completion.

Citations

Information excerpted from the CMGCC website; additional information can be found there.

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Background

The Collaborative Cross (CC) is a multiparent panel of recombinant inbred mouse strains derived from eight founder laboratory strains: 129S1/SvImJ, A/J, C57BL/6J, NOD/ShiLtJ, NZO/HlLtJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ. These strains include three major Mus musculus subspecies (M. m. musculusM. m. domesticus, and M. m. castaneus) and an extraordinarily high level of genetic diversity. Prior to their relocation to UNC, the CC project involved breeding at Oak Ridge National Laboratory in the United States, Geniad LLC in Australia, and Tel Aviv University in Israel.

This reproducible panel is uniquely suited for systems genetics and the study of complex traits. The CC panel is also a valuable source of novel laboratory models of human diseases. Additional information, including genotype and sequence data of CC strains, can be found in the related links section below.

MMRRC Holdings

In collaboration with the UNC-Systems Genetic Core Facility, the MMRRC at UNC has 63 strains available for distribution. View the MMRRC-UNC catalog of all CC strains here. Due to the wide range reproductive performance of these strains, the shipment time and batch size may vary. Users must contact mmrrc_cc@unc.edu to consult on experimental design and individual availability to select strains that will be most useful for their studies.

Distribution

The Collaborative Cross Conditions of Use can be found here. Mice can be purchased for breeding stock (for internal use only) or as experimental cohorts. 

Related Links

  • Genotype and haplotype information from the definitive obligate ancestors (Most Recent Common Ancestors, MRCA) of CC mice sent from the UNC Systems Genetics Core Facility (SGCF) can be found here.
  • Whole genome sequence from individual male animals from each strain in the SGCF as of 2015-2017, as well as detailed genotype and haplotype data from these individual mice are available. Summary information can be found here. More detailed information is included in the data associated with two papers (2017 with 69 strains - here, and 2019 with 6 additional strains - here).
  • Users can query the CC distributable strains at a specific gene, marker, or locus to identify founders at that locus using the tool located here.

Background

The Collaborative Cross (CC) is a multiparent panel of recombinant inbred mouse strains derived from eight founder laboratory strains: 129S1/SvImJ, A/J, C57BL/6J, NOD/ShiLtJ, NZO/HlLtJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ. These strains include three major Mus musculus subspecies (M. m. musculusM. m. domesticus, and M. m. castaneus) and an extraordinarily high level of genetic diversity. Prior to their relocation to UNC, the CC project involved breeding at Oak Ridge National Laboratory in the United States, Geniad LLC in Australia, and Tel Aviv University in Israel.

This reproducible panel is uniquely suited for systems genetics and the study of complex traits. The CC panel is also a valuable source of novel laboratory models of human diseases. Additional information, including genotype and sequence data of CC strains, can be found in the related links section below.

MMRRC Holdings

In collaboration with the UNC-Systems Genetic Core Facility, the MMRRC at UNC has 63 strains available for distribution. View the MMRRC-UNC catalog of all CC strains here. Due to the wide range reproductive performance of these strains, the shipment time and batch size may vary. Users must contact mmrrc_cc@unc.edu to consult on experimental design and individual availability to select strains that will be most useful for their studies.

Distribution

The Collaborative Cross Conditions of Use can be found here. Mice can be purchased for breeding stock (for internal use only) or as experimental cohorts. 

Related Links

  • Genotype and haplotype information from the definitive obligate ancestors (Most Recent Common Ancestors, MRCA) of CC mice sent from the UNC Systems Genetics Core Facility (SGCF) can be found here.
  • Whole genome sequence from individual male animals from each strain in the SGCF as of 2015-2017, as well as detailed genotype and haplotype data from these individual mice are available. Summary information can be found here. More detailed information is included in the data associated with two papers (2017 with 69 strains - here, and 2019 with 6 additional strains - here).
  • Users can query the CC distributable strains at a specific gene, marker, or locus to identify founders at that locus using the tool located here.

Background

The Consortium for Functional Glycomics (CFG) is a large research initiative, funded by the National Institute of General Medical Sciences, and formed to define the paradigms by which protein-carbohydrate interactions mediate cell communication. The strategy to achieve this goal is to work with the scientific community to create unique resources and services that Participating Investigators can utilize in their own research. Data produced by the Scientific Cores, much of which is generated using samples provided by investigators, are uploaded into the CFG relational database, the primary vehicle for integrating data across platforms and for dissemination of data to investigators and to the scientific community. Specialty databases for glycan-binding proteins, glycan structures, and glycosyltransferases are available. The Mouse Core (G) targeted multiple associated genes to generate a collection of knockout and conditional knockout mutant models.

MMRRC Holdings

These mice and materials were deposited to the MMRRC by the Consortium for Functional Glycomics. The MMRRC currently holds 24 mouse models and several ES cell lines from this collection and the MMRRC at UC Davis will generate an additional group of mouse models for this collection from the supplied ES cells. View MMRRC catalog of all Consortium for Functional Glycomics lines.

Distribution

Mutant mouse and cell lines are distributed using the MMRRC Conditions of Use* (COU). Mice are available only to investigators at non-profit institutions.

*The preceding link is to the COU text only; the COU user form will be provided after order submission.

If you publish using these mice or materials, please add the following statement to the acknowledgement section of your submitted manuscripts:

The authors wish to acknowledge the NIH-sponsored Mutant Mouse Regional Resource Center (MMRRC) National System as the source of genetically-altered (mice and/or materials) for use in this study, (please insert strain name and stock number here). The (mice or materials) were produced and deposited to the MMRRC by the Consortium for Functional Glycomics supported by the National Institute of General Medical Sciences (GM62116).

Citations

Information on this page has been excerpted from the CFG Nature Functional Glycomics Gateway website. Please acknowledge CFG in publications. Here are examples of how to acknowledge the CFG in a publication.

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Background

The participating research centers of the CvDC are using a variety of genome-wide approaches to build a higher-order cardiac development network model. Using forward genetic screening in mice will expand the number of mutant mouse lines that display phenotypes at the stages most relevant for human heart defects. Selected candidate molecules identified by the high-throughput techniques will be functionally validated by perturbation studies and subsequent characterization. Through interactions with its sister groups in the Bench to Bassinet program, the CvDC will identify and pursue those basic discoveries in cardiac regulatory networks with the greatest potential to translate to clinical applications for treatment and prevention.

These biallelic mutant mice from Dr. William T. Pu at Boston Children’s Hospital possess a FLAG/bio epitope tag downstream of the 3' UTR of the targeted gene and the Gt(ROSA)26Sortm1(birA)Mejr allele, which expresses HA (hemagglutinin) tagged bacterial birA, bifunctional protein (biotin ligase). In the double mutant mice, the targeted gene is biotinylated, allowing for its specific immunoprecipitation and any bound proteins.

MMRRC Holdings

The MMRRC holds 7 mutant strains in this collection. View the MMRRC catalog listing of all CvDC/B2B lines.

Background

On October 5, 2005, NIH announced that contracts had been signed with two companies, Deltagen, Inc. and Lexicon Genetics, Inc., to provide knockout mouse lines and extensive phenotyping data on them to NIH. This resource gives researchers unprecedented access to two private collections of knockout mice, providing valuable models for the study of human disease and laying the groundwork for a public, genome-wide library of knockout mice. The contracts also provide the opportunity for NIH to obtain up to 1500 additional mouse lines and phenotypic data over the next three years, pending available funds.

Deltagen targeted knockouts are constructed by homologous recombination and created in-house on consistent background strains. Most are on C57BL/6. Unlike random mutagenesis or gene trap approaches, the propriety methodology ensures a single targeted gene deletion or knockout event.

For each mouse line, Deltagen provided the mouse strain, but also detailed, objective data on the impact of the specific gene deletion on the mouse's phenotype, which includes appearance, health, fitness, behavior, ability to reproduce, and radiological and microscopic data. These detailed phenotypic data are available from the Mouse Genome Informatics (MGI) website, and a link to the data for each strain is provided in the MMRRC Strain Data Sheet. Such comprehensive information on such a large group of mice has never been available to public sector researchers and is expected to greatly accelerate efforts to explore gene functions in health and disease.

For each mouse line, frozen embryos, sperm, and embryonic stem (ES) cells were obtained under the contract. The materials were divided between the NIH-sponsored Mutant Mouse Regional Resource Centers (MMRRC) facility at the University of North Carolina and The Jackson Laboratory. The repositories expanded and archived these materials.

MMRRC Holdings

The MMRRC holds over 40 mutant strains produced by Deltagen in this collection. View MMRRC catalog of all Deltagen lines.

Distribution

The Delatagen contract provides NIH with irrevocable, perpetual, worldwide, royalty-free licenses to use and distribute to academic and non-profit researchers these lines of knockout mice. The mouse lines, most of which are stored in the form of frozen embryos, frozen sperm and frozen embryonic stem (ES) cells, are distributed using a Deltagen Standard Academic License Agreement.

Under the license agreement with Deltagen, researchers who receive the knockout mice lines through NIH are free to publish any results from research involving the line and also to seek patent or other intellectual property protection for any of the inventions or discoveries resulting from such research.

Citations

Information excerpted from the Deltagen website; additional information can be found there.

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Background

Collaboration between Genentech Inc. and Lexicon Pharmaceuticals Inc. created a mouse knockout library targeting genes encoding secreted and trans-membrane proteins. These efforts generated a collection of 472 mouse models specific to this project. “The knockout mice were subjected to a broad, unbiased phenotypic screen aimed at identifying potential defects in general metabolism, in bone metabolism, or in the function of the cardiovascular, the immune or the neural systems.” This collection of knockout mouse models, corresponding allele information and derived data was donated to the MMRRC for distribution to the scientific community. This valuable research resource includes several hundred unique lines that further enhance the goals of the KOMP Initiative.

MMRRC Holdings

The MMRRC at UC Davis received 604 strains for a total of 495 mutant alleles, including the secreted and trans-membrane protein models, and knockout models targeting 23 other genes from the Genentech and Lexicon Pharmaceutical collaboration. Many of the strains received have been made congenic, including 87 alleles on a C57BL/6NCrl background, and several on other backgrounds including BALB/cJ and 129S6/SvEvTac. View MMRRC catalog of all Genentech Lexicon lines.

Distribution

The mouse models from this collection are distributed using the Genetech Lexicon Material Transfer Agreement. Distribution is limited to Non-profit academic and government institutions only. For-profit entities please contact mmrrc@ucdavis.edu and they will forward your interest to the appropriate party.

Citations

Information here is excerpted from the following publication: A mouse knockout library for secreted and transmembrane proteins, Tang T, et al, Nature Biotechnology, advanced online publication 20 June 2010 (DOI 10.1038/nbt.1644)

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Background

The GENSAT project aims to map the expression of genes in the central nervous system of the mouse, using in situ hybridization and transgenic mouse techniques. The GENSAT project is sponsored through a contract with the National Institute of Neurological Disorders and Stroke (NINDS). The principal investigators of the study are Nathaniel Heintz, Ph.D., and Mary E. Hatten, Ph.D., Professors, Rockefeller University.

The GENSAT collection contains transgenic strains of mice in which each transgene is derived from bacterial artificial chromosomes (BACs) and expresses a reporter gene in the same environment as the native gene. In each of the BAC transgenic vectors, endogenous protein coding sequences have been replaced by sequences encoding the EGFP reporter gene. As in any gene replacement experiment, the stability of the reporter gene can vary somewhat from the endogenous gene. Thus these results measure the relative rates of transcription for each gene; they are not a direct measure of mRNA accumulation or of protein abundance for the endogenous gene products. Furthermore, the enhanced sensitivity of reporter gene assays, particularly in BAC lines carrying multiple copies of the BAC transgene may allow detection of sites of expression that are not evident in in situ hybridization experiments.

In conjunction with these strains, several cre transgenic strains have been created where BAC engineering was used to insert an intron containing cre or creERT2 cassettes, followed by a polyadenylation sequence to terminate transcription of the fusion transcript immediately after the recombinase gene, into the BAC vector at the initiating ATG codon in the first coding exon of the gene.

The GENSAT database contains histological data from given BAC transgenic mouse lines at three developmental stages – embryonic day 15.5 (E15.5), postnatal day 7 (P7) and adult; in all cases the data represent results of multiple transgenic lines. A link to the data for each strain is provided in the MMRRC Strain Data Sheet. EGFP is visualized by staining with an anti-EGFP antibody using the DAB method, or by confocal microscopy of unstained tissue sections. Protocols for the modification of BACs, BAC transgenesis production, and histology are available at the GENSAT website; a complete description of the procedure can be found in "A gene expression atlas of the central nervous system based on bacterial artificial chromosomes", Nature. 2003 Oct 30;425(6961):917-25.

The recommended citation for the resource is:
The Gene Expression Nervous System Atlas (GENSAT) Project, NINDS Contract # N01NS02331 to The Rockefeller University (New York, NY).

MMRRC Holdings

The MMRRC holds over 1,300 strains in this collection and the number continues to grow. View MMRRC catalog of all GENSAT lines

Distribution

Strains are distributed using the MMRRC Conditions of Use *(COU). Mice are available only to investigators at non-profit institutions.
* The preceding link is to the COU text only; the COU user form will be provided after order submission.

Citations

Information excerpted from the GENSAT website; additional information can be found there.

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Background

The Noncoding RNA project was developed by the Michael McManus Lab in collaboration with colleagues at UCSF and the Gladstone Institute.
Using genome-scale RNA interference (RNAi) screening and other high-throughput methodologies to uncover the functions of noncoding RNAs in the mammalian system, the McManus Lab has generated and characterized many small (micro) RNA conditional knockout mice. These mouse models could shed light on a wide range of human diseases such as diabetes, many types of cancers, and even neurological diseases such as depression.
Each miRKO targeting vector is designed to insert an FRT site followed by a lacZ gene, a loxP site, a neomycin cassette, an FRT site and a loxP site (FRT-lacZ-loxP-Neo-FRT-loxP) upstream of the stem loop, with one loxP site placed immediately downstream of the Mir (microRNA) stem loop. When a Mir strain is combined with a Flp recombinase-expressing strain, the lacZ and neomycin genes are removed leaving an FRT site and the loxP-flanked Mir stem loop. A further cross to a Cre-recombinase-expressing strain generates the null allele. When combined with a Cre-recombinase-expressing strain, the neomycin cassette and Mir stem loop are removed leaving a lacZ tagged null allele (FRT-lacZ-loxP). These miRKO models provide a tool for understanding how noncoding RNAs contribute to the specification of cell fate and function, and how deregulation of these RNAs may contribute to human disease.


MMRRC Holdings

This collection has approximately 58 ES cell lines and 44 mouse lines archived. Products available in the Keck miRNA Knockout Collection are listed in the following links.

MMRRC catalog of all Keck miRNA knockout lines

  • ES cell lines are maintained at the MMRRC at UC Davis. For additional assistance with the ES cell lines, please contact the MMRRC at UC Davis at (530) 754-3290 or email mmrrc@ucdavis.edu.
  • Resuscitation to live mice and sperm are available at the MMRRC at JAX. For additional assistance with the mouse l lines, please contact the MMRRC at The Jackson Laboratory at (855) 240-8336 or email csmmrrc@jax.org.
Distribution

Cells and mice from this collection are distributed using the MMRRC Conditions of Use *(COU), and are available only to investigators at non-profit institutions
* The preceding link is to the COU text only; the COU user form will be provided after order submission.
For additional assistance, please contact the Service@MMRRC.org at (800) 910-2291

Citations

Information here is excerpted from the following where additional information can be found.

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Background

The Knockout Mouse Project (KOMP & KOMP2) is a trans-NIH initiative that aims to generate a comprehensive and public resource comprised of mouse embryonic stem (ES) cells containing a null mutation in every gene in the mouse genome. The NIH KOMP initiative aims to:

  1. use gene targeting to make the resource of null alleles, marked with a high utility reporter, preferably in C57BL/6;

  2. support a repository to house the products of this resource as well as an additional repatriation' effort to bring into repositories 1000 of the existing high priority mouse knockouts not already stored in a public repository;

  3. develop improved C57BL/6 ES cells that show robust germline transmission, so that they may be used in a high throughput pipeline in generating this resource; and 

  4. implement a data coordination center which will make the status and relevant data of the production effort available to the research community.

Towards those ends, NIH awarded five-year cooperative agreements totaling up to $47.2 million to two groups for the creation of the knockout mice lines. Recipients of those awards are Velocigene, a division of Regeneron Pharmaceuticals, Inc., in Tarrytown, N.Y., and a collaborative team from Children's Hospital Oakland Research Institute (CHORI) in Oakland, Calif., the School of Veterinary Medicine, University of California, Davis (UC Davis); and the Wellcome Trust Sanger Institute in Hinxton, England. Under its cooperative agreement, the team 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, plans to systematically create mouse ES cell lines in which 5,000 genes have been knocked out by gene targeting. The VelociGene division of Regeneron, led by David Valenzuela, Ph.D. and George D. Yancopoulos, M.D., Ph.D., will take aim at a different set of 3,500 genes. Both groups will utilize information from the finished mouse genome sequence to design targeting vectors, which will be built by large-scale, automated technologies. The combined collection of mouse ES cells with knockouts in 8,500 genes will be useful for producing knockout mice.

In addition, NIH awarded another five-year cooperative agreement totaling $2.5 million to Mouse Genome Informatics (MGI) to set up a Data Coordination Center for the Knockout Mouse Project. The center will collect information that will allow the research community to track the scheduling and progress of knockout production. 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.

Finally, in June 2007, NIH announced it will provide $4.8 million to establish and support a repository for its Knockout Mouse Project. 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. The University of California, Davis (UC Davis) and Children's Hospital Oakland Research Institute (CHORI) in Oakland, Calif., will collaborate to preserve, protect, and make available about 8,500 types of knockout mice and related products available to the research community.

MMRRC Holdings
The KOMP catalog compiles the collection's current holdings, which include live mice, wild-type and mutant embryonic stem cells, and germplasm. 
Related Links
Background

On October 5, 2005, NIH announced that contracts had been signed with two companies, Deltagen, Inc. and Lexicon Genetics, Inc. (now Lexicon Pharmaceuticals), to provide knockout mouse lines and extensive phenotyping data on them to NIH. This resource gives researchers unprecedented access to two private collections of knockout mice, providing valuable models for the study of human disease and laying the groundwork for a public, genome-wide library of knockout mice. The contracts also provide the opportunity for NIH to obtain up to 1500 additional mouse lines and phenotypic data over the next three years, pending available funds.

The Lexicon efforts are focused on gene families that are pharmaceutically important, such as transporters, G-protein coupled receptors (GPCRs), ion channels, kinases and other key enzymes, membrane proteins (e.g., receptors), and secreted proteins.

For each mouse line, Lexicon provided not only the mouse strain itself, but also detailed, objective data on the impact of the specific gene deletion on the mouse's phenotype, which includes appearance, health, fitness, behavior, ability to reproduce, and radiological and microscopic data. These detailed phenotypic data are available from the Mouse Genome Informatics (MGI) website, and a link to the data for each strain is provided in the MMRRC Strain Data Sheet. Such comprehensive information on such a large group of mice has never been available to public sector researchers, and is expected to greatly accelerate efforts to explore gene functions in health and disease.

For each mouse line, frozen embryos, sperm, and embryonic stem (ES) cells were obtained under the contract. The materials were divided between the NIH-sponsored Mutant Mouse Regional Resource Centers (MMRRC) facilities at UC Davis and the University of North Carolina.

MMRRC Holdings

The MMRRC holds 125 mutant mouse strains and 123 ES cell lines produced by Lexicon in this collection. View MMRRC catalog of all Lexicon lines.

Distribution

The Lexicon contract provides NIH with irrevocable, perpetual, worldwide, royalty-free licenses to use and distribute to academic and non-profit researchers these lines of knockout mice. The mouse lines, most of which are stored in the form of frozen embryos, frozen sperm and frozen embryonic stem (ES) cells, are distributed using a Lexicon simple Letter Agreement.

Under the license agreement with Lexicon, researchers who receive the knockout mice lines through NIH are free to publish any results from research involving the line and also to seek patent or other intellectual property protection for any of the inventions or discoveries resulting from such research.

Citations


Related Links
Background

This collection, assembled and maintained by Dr. Lynn Lamoreux while at Texas A&M University, contains pigment mutant mouse strains, virtually all as congenic strains on a C57BL/6 background. These numerous pigmentary mutations, individually and in appropriate combinations, enable the rigorous evaluation of mutations at the organism, organ and tissue levels, and the assessment of genic interactions. The collection was created to help investigators achieve a complete understanding of the genetic control of development and function of the mammalian pigmentation system and its diseases, including interacting functions that affect other biological systems by pleiotropic effects.

Pigmentation and the pigment cell form an ideal system for genetic analysis of a developmental system, since pigmentary mutations are readily detected and most often are not lethal. Rich genetic resources exist for study of mouse pigmentation: germline mutations mapped now to over 120 loci, around 50 of which have been cloned. These mutations are also relevant to melanoma and to numerous associated birth defects of organs including the ear, eye, brain, reproductive, digestive and respiratory tracts, hemophilia, and cellular defects in protein transport, organelle biogenesis and apoptosis.

Cell lines from many of these mutants have been made and can be obtained from the Wellcome Trust Functional Genomics Cell Bank. These melanocyte and melanoblast lines, carrying diverse pigmentary mutations, are used to study gene functions at the cellular, biochemical and molecular levels.

MMRRC Holdings

The MMRRC holds 50 mutant strains in this collection. View MMRRC catalog of all Mammalian Pigmentation lines.

Distribution

Strains are distributed using the MMRRC Conditions of Use *(COU).

* The preceding link is to the COU text only; the COU user form will be provided after order submission.

Related Links
Background

The goal of the ENU Mutagenesis project is to determine the function of genes on mouse Chromosome 11 by saturating the chromosome with recessive mutations. The distal 40 cM of mouse Chromosome 11 exhibits linkage conservation with human Chromosome 17. The chemical N-ethyl-N-nitrosourea (ENU) was used to saturate wild type chromosomes with point mutations. By determining the function of genes on a mouse chromosome, extrapolation leads to predicting function on a human chromosome. Many of the new mutants are expected to represent models of human diseases such as birth defects, patterning defects, growth and endocrine defects, neurological anomalies, and blood defects. Because many of the mutations expected to be isolated may be lethal or detrimental to the mice, a unique approach to isolate mutations is used. This approach uses a balancer chromosome that is homozygous lethal and carries a dominant coat color marker to suppress recombination over a reasonable interval.

MMRRC Holdings

The MMRRC holds over 30 strains in this collection. View MMRRC catalog of all Mutagenesis for Dev. Defects/Baylor lines.

Distribution

Strains are distributed using the MMRRC Conditions of Use *(COU). Most, but not all, Mutagenesis for Developmental Defects/Baylor strains are restricted to investigators at non-profit institutions.

* The preceding link is to the COU text only; the COU user form will be provided after order submission.

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Background

The Nagy ES cell collection is a panel of basic ES cells that can be used for gene targeting. Two of the lines are from inbred C57BL/6 and the others are either 129 x 129 or 129 x B6 F1 hybrids. Several carry fluorescent reporter transgenes that enable one to follow the cell lines in chimeras.

MMRRC Holdings

The MMRRC holds 14 cell lines for this resource. View MMRRC catalog of all Nagy Basic ES Cell Lines

Distribution

Cell lines are distributed using the MMRRC Conditions of Use *(COU). These cell lines are available only to investigators at non-profit institutions.

* The preceding link is to the COU text only; the COU user form will be provided after order submission.

Citations

Information excerpted from the Nagy website; additional information can be found there.

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Background

The NIH Neuroscience Blueprint has established three centers in the USA for the generation of genetically modified mice expressing Cre recombinases in the nervous system on the C57BL/6 genetic background. The mouse lines are being generated at the Baylor College of Medicine, Cold Spring Harbor Lab, and Scripps Research Institute. Mice are being made available via the Mutant Mouse Regional Resource Centers facility at the University of Missouri and The Jackson Laboratory Cre Repository.

MMRRC Holdings

The MMRRC holds over 15 strains in this collection and the number continues to grow. View MMRRC catalog of all Neuroscience Blueprint cre lines.

Distribution

Strains are distributed using the MMRRC Conditions of Use *(COU). Mice are available only to investigators at non-profit institutions.

* The preceding link is to the COU text only; the COU user form will be provided after order submission.

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Background
The NHMRC Australian PhenomeBank (APB) is a non-profit repository of mouse strains housed and archived in Australia. This collection of ENU strains generated by Dr. Chris Goodnow, of Australian National University, with support of NIH funding has been donated to the MMRRC meeting the obligations to NIH by making them available to researchers in the US and worldwide.
The APB strains were produced through random germline mutagenesis with ENU. Where possible, value is added by focusing on sets of genes that serve related biological functions, and offering insight into the mechanism by which phenotypes arise. The MMRRC Strain Detail Sheets link to the APB strain records that contain additional information on cDNA sequences and/or genomic DNA sequences in the NCBI database.
MMRRC Holdings

The MMRRC holds >150 mouse models from this collection at the MMRRC at UC Davis. View MMRRC catalog of all Australian PhenomeBank strains.

Distribution

Strains are distributed using the MMRRC Conditions of Use *(COU), and are available only to investigators at non-profit institutions.

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Background

These mice were created and deposited by The Pleiades Promoter Project (Centre for Molecular Medicine and Therapeutics, University of British Columbia); their goal is to generate 160 fully characterized, human DNA promoters of less than 4 kb (MiniPromoters) to drive gene expression in defined brain regions of therapeutic interest for studying disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic Lateral Sclerosis (Lou Gehrig's disease), Multiple Sclerosis, Spinocerebellar Ataxia, Depression, Autism, and Cancer.

MMRRC Holdings

The MMRRC holds over 1100 ES cell lines and 49 mutant strains in this collection.

MMRRC catalog of all Pleiades Promoter Project lines.

Distribution

Mutant mouse and cell lines are distributed using the MMRRC Conditions of Use* (COU). Mice are available only to investigators at non-profit institutions.
*The preceding link is to the COU text only; the COU user form will be provided after order submission.

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Background

  With the advent of CRISPR/Cas9 genome editing technology, the ability to manipulate the genomes of animals to enhance their relevance to human biology and disease has dramatically expanded.  Recognizing the potential for advancing translational research using this new methodology, over the last few years the NIH has launched new programs and awarded administrative supplements to existing grants to enable the production and phenotyping of animal models that recapitulate human coding sequences associated with and/or directly causative of disease. For example, in 2018 the NIH/Office of the Director funded an administrative supplement to the MMRRC at UC Davis to create and study ~20 mouse models of specific genetic variants to determine their relationship to disease phenotypes in patients. More recently, the NIH funded projects to produce and phenotype mouse models of SARS-CoV-2 infection and COVID-19, especially post-acute sequelae of COVID, or PASC, that express human-specific coding sequences in orthologous mouse genes directly involved in disease pathogenesis (e.g., ACE2, TMPRSS2, etc).  These and other projects have generated human disease-relevant mouse models for pre-clinical and co-clinical biomedical research. To ensure their availability and accessibility, the MMRRC has established this “Precision Genetically-Humanized Models” produced by NIH-funded researchers.

MMRRC Holdings

 The MMRRC holds dozens of strains in this collection which are added to regularly. View the MMRRC catalog of Precision Genetically-Humanized Models.

Distribution

Strains are distributed using the MMRRC Conditions of Use *(COU). Depending on funding circumstances and prior agreements, distribution of some models might be restricted to investigators at non-profit institutions.

* The preceding link is to the COU text only; the COU user form will be provided after order submission.

 
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Background

MicroRNAs (miRNA) are gaining recognition as important post-transcriptional regulators of gene expression. While more than 500 miRNAs have been identified in the mammalian genome, studies addressing their physiological roles are at an early stage and miRNA functions are only now being elucidated. Toward this end, the Sanger Institute is generating a continually expanding collection of MicroRNA Knockout ES cell lines for use by the scientific community through the MMRRC. Additionally, Sanger has created a searchable data portal through which investigators can access additional information such as vector design, PCR results, and gene details. Schematic of MirKO targeting vector and alleles

MMRRC Holdings

In the first shipment from Sanger, the MMRRC at UC Davis received 10 96-well plates containing a total of 614 distributable ES cell clones, and will receive additional clones as they are generated. There are approximately 154 different MicroRNA encoding genes represented. The majority of these clones were generated on a JM8A3 background with a small percentage of clones generated on a JM8.F6 background. A subset of these miRNA knockout lines are “cluster” knockouts in which more than one gene has been targeted. The MMRRC catalog pages for these strains indicate the presence of a cluster and strains are named according to the first gene in the cluster.

Requesters should be aware that there are some clones for which it has not been possible to confirm targeting by PCR at both ends. This is most likely due to technical failure of the PCR rather than incorrectly targeted clones; however, investigators are strongly encouraged to confirm targeting by Southern Blot analysis. The MMRRC catalog pages for these strains will note PCR failure where applicable.

The MMRRC holds over 100 lines in this collection. View MMRRC catalog of all Sanger miRNA knockout lines

Distribution

Cells from this collection are distributed using the MMRRC Conditions of Use *(COU). Cells are available only to investigators at non-profit institutions.

* The preceding link is to the COU text only; the COU user form will be provided after order submission.

For additional assistance with these clones, please contact the MMRRC at UC Davis at (530) 754-3290 or email mmrrc@ucdavis.edu.

Citations

Information here is excerpted from the following publication:

  • Prosser HM, Koike-Yusa H, Cooper JD, Law FC, Bradley A. A resource of vectors and ES cells for targeted deletion of microRNAs in mice. Nature Biotechnology 2011, 29(9):840-5 (PMID:21822254).
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Background

The Sanger Institute Gene Trap Resource (SIGTR) mouse ES cell line collection was developed to provide a powerful and cost effective approach using gene trapping to create large numbers of insertional mutations that are immediately accessible to molecular characterization. This resource is based on a new generation of gene trap vector designs that are equipped with site-specific recombination sites for post-insertional modification of the trapped locus to create other desired alleles.

Users of SIGTR ES cell lines are advised to follow the protocols available on the SIGTR website. In addition to individual protocols, all the procedures and protocols can be downloaded from the General Information section of SIGTR's website. Detailed information contained there includes:

  • Molecular confirmation of gene trap insertions
  • Cell culture media and reagent preparation
  • Thawing and growing feeder-independent ES cell lines
  • X-gal staining of ES cells
  • Sub-cloning gene trap cell lines
MMRRC Holdings

The MMRRC holds over 11,800 lines in this collection. View MMRRC catalog of all SIGTR lines

Distribution

Sanger Institute Gene Trap Resource (SIGTR) ES Cell Lines are distributed using the Sanger Institute Gene Trap Resource (SIGTR) COU.

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Background

To identify growth factor regulated genes, gene traps are used in embryonic stem (ES) cells. In this approach, a promoterless reporter gene (for instance encoding beta galactosidase, or beta geo) is introduced into ES cells. Selection for expression of the gene requires transcription from a cellular promoter, and consequently a mutation in a cellular gene, and the activity of the tagged gene can be followed by staining for beta galactosidase activity. Detailed description of methods used for gene trap mutagenesis may be found in Friedrich, G., and Soriano, P. (1993) and Chen, W.V., and Soriano, P. (2003). Large scale sequencing of ES cell clones was conducted and sequence tags have been deposited to NCBI's dbGSS. Sequence searches for genes that have been trapped can be performed by running a BLAST search of the dbGSS database.

The recommended citations for the resource are:
Friedrich, G., and Soriano, P., Methods Enzymol. 1993;225:681-701 (PMID:8231879)
Chen, W.V., and Soriano, P., Methods Enzymol. 2003;365:367-86 (PMID:14696359)

MMRRC Holdings

The MMRRC holds over 1,200 cell lines for this resource. View MMRRC catalog of all Soriano Gene Trap Lines lines.

Distribution

Cell lines are distributed using the MMRRC Conditions of Use *(COU).

* The preceding link is to the COU text only; the COU user form will be provided after order submission.

Citations

Information excerpted from the Soriano website; additional information can be found there.

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Background

The mission of the UC Davis/NIH NeuroMab Facility is to provide a unique neuroscience-based approach to generating mouse monoclonal antibodies optimized for use in the mammalian brain. The UC Davis/NIH NeuroMab Facility serves as a resource to the entire neuroscience community through its generation of a collection of highly validated antibodies that serve as critical links between information emerging from genomic efforts and future proteomic approaches to brain function.

Hybridoma cell lines are immortal, monoclonal, antibody-producing cells that can be grown in tissue culture at any scale to produce monoclonal antibodies. Each of the 473 cell lines in the MMRRC were use to produce monoclonal antibodies that have been validated for specificity and efficacy in brain research applications at the UC Davis/NIH NeuroMab Facility.

This collection empowers researchers with the ability to produce large quantities of specific and highly validated monoclonal antibodies at a low cost. Conveniently, the MMRRC also provides access to knockout mouse lines for genes that encode protein targets of the NeuroMab monoclonal antibodies.

MMRRC Holdings
The MMRRC currently holds over 470 hybridoma lines in this collection. For a list of all NeuroMab hybridoma line holdings at the MMRRC, click here

Distribution
Please cite the "UC Davis/NIH NeuroMab Facility" as the source and include the complete clone number (e.g., N52A/42) as well as the Antibody Registry identification number (e.g., RRID:AB_2120479). All lines are distributed under defined Conditions of Use (COU); the COU user form will be provided after order submission. The lines are available only to investigators at non-profit institutions. 

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