MMRRC Best Practices

The purpose of this page is to outline and describe best practices that guide the operations, management, decision-making, and future planning of the Mutant Mouse Research and Resource Center (MMRRC) Consortium. In this context, best practices are defined as actions, procedures, methods, and/or processes that have proven to be most effective in evaluating, maintaining, verifying, and distributing mutant and other mouse models for biomedical research. MMRRC best practices consider all relevant aspects of species-specific biology, physiology, and behavior, are based on the best available scientific evidence or accepted practices and include strategies to minimize potential adverse impact of conditions and procedures on animal care and welfare, safety, recoverability, utility and reliability of mouse resources for rigorous and reproducible biomedical research. Areas of MMRRC Consortium activities guided by best practice principles include 1) Identification and nomenclature, 2) Husbandry, welfare, and protection from adventitious pathogens, 3) Genotype and/or phenotypic verification, 4) Integrity and reliability of cryopreservation and cryorecovery processes and safety and sustainability of the cryoarchive, 5) Relevance and relatedness to biology and/or disease research, 6) Fulfillment of ARRIVE2 and PREPARE guidelines for animals used for research, and 7) Scientific and technical support and breadth and depth of extended resources for users. MMRRC best practices are overseen, written, reviewed, and revised by the MMRRC Rigor and Reproducibility Committee.

  1. Identification and nomenclature: The MMRRC ensures mice for a line that are accepted for deposition, maintenance, and distribution are described (e.g., number, sex, observable phenotype) and marked or otherwise physically annotated (e.g., toe snips, ear punch, ear tag) in a unique manner sufficient to distinguish all mice within the line. Further, the MMRRC reviews and, if needed, revises the identifying name of the mouse line using the current version of internationally recognized standards of nomenclature (Mouse Genome Informatics, [MGI] version 6.17; http://www.informatics.jax.org/mgihome/nomen/index.shtml). Finally, the MMRRC, if necessary, assigns a unique Research Resource Identifier (RRID; https://scicrunch.org/resources) to each mouse line. This activity is written, overseen, reviewed, and revised by the MMRRC Operations, Health, and Management Committee and the MMRRC Rigor and Reproducibility Committee.
  2. Husbandry, welfare, and protection from adventitious pathogens: The MMRRC follows the current version of the National Research Council Guide for the Care and Use of Laboratory Animals (8th Edition; https://www.ncbi.nlm.nih.gov/books/NBK54050/) and adheres to all accreditation requirements of the American Association for Laboratory Animal Sciences (AALAS; https://www.aalas.org/) for husbandry, welfare, and protection from adventitious pathogens of mice maintained and distributed from its member distribution repositories. This activity is written, overseen, reviewed, and revised by the MMRRC Operations, Health, and Management Committee.
  3. Genotype and/or phenotype verification: The MMRRC uses standard and recognized techniques and methods (e.g., end-point polymerase chain reaction [PCR], DNA sequencing and analysis) to detect the presence and zygosity of the mutant (e.g., transgenic, gene targeted, etc) allele(s) specific and unique to each mouse line. In addition to gene-specific genotyping, the MMRRC uses a mouse universal genotyping array (MUGA; https://csbio.unc.edu/MUGA/) to verify and quantify the diversity of genetic backgrounds and the presence and/or absence of specific exogenous alleles. In cases in which genetic analysis is not possible, then the MMRRC will apply a phenotype test or procedure to specifically identify and distinguish a mouse line. The unique genotyping and/or phenotyping characteristics verified by the MMRRC will be described in the online strain detail sheet (SDS) page associated with the mouse line. This activity is written, overseen, reviewed, and revised by the MMRRC Genetics Committee and the MMRRC Metagenomics Committee.
  4. Integrity and reliability of cryopreservation and cryorecovery processes and safety and sustainability of the cryoarchive: All mouse lines accepted as live mice for maintenance and distribution by the MMRRC are subject to creation of a cryopreserved germplasm (sperm and/or embryos) archive. Cryopreservation procedures follow accepted published guidelines and must ensure sustained preservation and recovery to a live mouse that recapitulates the genotype and/or phenotype of the originally cryopreserved mouse line. Mouse lines that are accepted as frozen germplasm are genotypically verified (see “3” above) and proven cryorecoverable either individually or as part of a batch validation of cryorecovery. Embryonic stem cell (ESC) clones, hybridomas, and other cell lines are verified either directly (e.g., genotypically) or by associated unique identifiers provided by the depositor. Finally, the cryopreserved archive of a mouse line must be physically split into at least two distinct and separate locations in a manner which ensures the protection from loss of the mouse line. This activity is written, overseen, reviewed, and revised by the MMRRC Cryobiology Committee.
  5. Relevance and relatedness to biology and/or disease research: Mouse lines accepted by the MMRRC must be associated with data, images, or information upon submission (e.g., direct entry into the submission documents, associated publications) that indicate the relevance and relatedness to biology and/or disease research. Depositors will be asked to provide additional and/or clarifying information if needed to enable a clear and unambiguous understanding of the scientific value of the mouse line for biomedical research. This activity is written, overseen, reviewed, and revised by the MMRRC Coordinating Committee.
  6. Fulfillment of ARRIVE2 and PREPARE guidelines for animals used for research: The MMRRC ICSC will provide customers obtaining MMRRC resources with information on and answer questions regarding standardized guidelines that emphasize the appropriate planning of experiments (Planning Research and Experimental Procedures on Animals: Recommendations for Excellence [PREPARE]; https://pubmed.ncbi.nlm.nih.gov/28771074/) and reporting of experimental results (Animal Research: Reporting of In Vivo Experiments [ARRIVE2]; https://arriveguidelines.org/arrive-guidelines) related to research using mice. This activity is written, overseen, reviewed, and revised by the MMRRC Rigor and Reproducibility Committee.
  7. Scientific and technical support and breadth and depth of extended resources for users: Upon acceptance, the MMRRC assumes the responsibility to maintain, preserve, protect, secure, and disseminate of all deposited mouse lines. To do so, individual members of the MMRRC operate using the aforementioned best practices, follows all appliacable guidelines, innovates newer and improved technologies, and engages in research to ensure the sustainability and scientific value of its resource holdings as long as it is funded by the NIH. This activity is written, overseen, reviewed, and revised by the MMRRC Coordinating Committee and the MMRRC Public Relations Committee.