The Mutant Mouse Resource and Research Center (MMRRC): the NIH-supported National Public Repository and Distribution Archive of Mutant Mouse Models in the USA

Abstract

The Mutant Mouse Resource and Research Center (MMRRC) Program is the pre-eminent public national mutant mouse repository and distribution archive in the USA, serving as a national resource of mutant mice available to the global scientific community for biomedical research. Established more than two decades ago with grants from the National Institutes of Health (NIH), the MMRRC Program supports a Consortium of regionally distributed and dedicated vivaria, laboratories, and offices (Centers) and an Informatics Coordination and Service Center (ICSC) at three academic teaching and research universities and one non-profit genetic research institution. The MMRRC Program accepts the submission of unique, scientifically rigorous, and experimentally valuable genetically altered and other mouse models donated by academic and commercial scientists and organizations for deposition, maintenance, preservation, and dissemination to scientists upon request. The four Centers maintain an archive of nearly 60,000 mutant alleles as live mice, frozen germplasm, and/or embryonic stem (ES) cells. Since its inception, the Centers have fulfilled 13,184 orders for mutant mouse models from 9591 scientists at 6626 institutions around the globe. Centers also provide numerous services that facilitate using mutant mouse models obtained from the MMRRC, including genetic assays, microbiome analysis, analytical phenotyping and pathology, cryorecovery, mouse husbandry, infectious disease surveillance and diagnosis, and disease modeling. The ICSC coordinates activities between the Centers, manages the website (mmrrc.org) and online catalog, and conducts communication, outreach, and education to the research community. Centers preserve, secure, and protect mutant mouse lines in perpetuity, promote rigor and reproducibility in scientific experiments using mice, provide experiential training and consultation in the responsible use of mice in research, and pursue cutting edge technologies to advance biomedical studies using mice to improve human health. Researchers benefit from an expansive list of well-defined mouse models of disease that meet the highest standards of rigor and reproducibility, while donating investigators benefit by having their mouse lines preserved, protected, and distributed in compliance with NIH policies.

Phenelzine-based probes reveal Secernin-3 is involved in thermal nociception

“…Therefore, we reasoned that a constitutive Scrn3 KO mouse model could be used to explore the functional significance of mammalian SCRN3 and its druggable Glox group in neurobiology. The discovery of Glox, which was impossible to predict from gene or protein sequence and harbored by proteins of unknown function (SCRN2 and SCRN3 but importantly, not SCRN1), made these genes ideal candidates for NIH’s Knockout Mouse Phenotyping Program (KOMP 2 ) (Amos-Landgraf et al, 2022). CRISPR-edited homozygous Scrn3 KO mice were generated and found to be viable and fertile.…”

Centralizing neurofibromatosis experimental tool knowledge with the NF Research Tools Database

“…Currently, this prototype database includes a variety of NF1-relevant research tools. We are working on curating additional NF1-relevant tools, such as mouse models listed in Mutant Mouse Research and Resource Centers (MMRRC) ( 7 ) and the European Conditional Mouse Mutagenesis Program ( 14 ), and more prepublication models provided by the research community, as well as NF2- and schwannomatosis-related tools to increase the comprehensiveness of the database. In addition, we plan to add a guided form-based submission system so that users can more easily contribute standardized data to the database, tune the search feature to improve results and develop a process to share collected data, when possible, from this database with the respective RRID-minting authorities (e.g.…”

“…Examples include foundational model system-specific databases, such as the Mouse Genome Informatics database ( 1 ), the Rat Genome Database ( 2 ), the Zebrafish Information Network ( 3 ) and the Saccharomyces Genome Database ( 4 ), and vendor catalogs that manufacture specific tools like antibodies, cell lines and genetic reagents. Recent efforts like the Resource Identification Initiative ( 5 ) integrate information for a wide variety of research tools, including cell lines via Cellosaurus ( 6 ), animal models via databases like Mutant Mouse Resource & Research Centers ( 7 ), antibodies via Antibody Registry ( 8 ) and reagents for genetic experiments (specifically, plasmids) via Addgene ( 9 ). The Resource Identification Initiative collaborates with these tool-specific authorities who assign research resource identifiers (RRIDs) to all of these research tools, enabling researchers to cite well-defined and curated records of specific tools.…”

Expression of LIM domain-binding 3 (LDB3), a striated muscle Z-band alternatively spliced PDZ-motif protein in the nervous system

“…Wild type mice (C57BL/6N) were from Charles River Laboratories (Wilmington, MA). LDB3 + /− mice (C57BL/6N-A tm1Brd /a Ldb3 tm2a(EUCOMM)Hmgu /BcmMmucd) were from the Mutant Mouse Resource & Research Center 40 . All mice were housed in the animal care unit of the National Institute of Neurological Disorders and Stroke (NINDS) according to the National Institutes of Health animal care guidelines.…”