MMRRC Reproducibility Assurances

The Mutant Mouse Resource & Research Centers (MMRRC), https://mmrrc.org is the NIH’s premier national consortium that provides the worldwide biomedical research community with access to more than 30,000 strains of mutant mice and ES cells. With one of the largest nonprofit repositories of mouse models in the world, the MMRRC distributes and archives models to advance the biomedical research efforts of the scientific research community. Each month through partnerships with researchers around the world, the MMRRC enhances critical research with a continuously expanding catalog of mouse models of human disease.

The MMRRC is your one stop resource for unique and popular research related mouse models offering specific gene deletions, insertions, modifications and repressions, and phenotypes.

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Advisory Committee to the NIH Director:
Enhancing Rigor, Transparency, and Translatability in Animal Research

The ACD Working Group was charged with assessing and making recommendations to enhance the rigor, transparency, and translatability in animal research by improving experimental design, optimizing translational validity, enhancing training, and increasing the transparency of research studies involving animal models.

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MMRRC Reproducibility & Rigor

Background

Over the past several years, there has been a growing awareness of the need for rigorously designed published research studies that are both transparent and reproducible. In response to this need, the National Institutes of Health (NIH) launched on January 25, 2016 a formal initiative aimed at improving research reproducibility through an emphasis on scientific rigor and transparency.

MMRRC’s Commitment to Optimizing Reproducibility

The MMRRC is committed to upholding the highest standards of experimental design and quality control to optimize the reproducibility of research studies using mutant mice. For example, understanding, documenting, and accurately reporting the genetic backgrounds of mouse models used in research is essential for recreating an experimental study and achieving reproducible results.

If research is to be reliable and reproducible, specific quality control and assurance testing need to be in place. This is why mouse models available from the MMRRC repository are annotated with well documented genetic backgrounds. Furthermore, because of our commitment to maintaining specific-pathogen-free vivaria and quality control measures, investigators can rely on mice obtained from the MMRRC to generate robust and reproducible results.

What is Scientific Rigor & Transparency?

Specifically, the NIH defines scientific rigor as “the strict application of scientific method to ensure unbiased and well-controlled experimental design, methodology, analysis, interpretation, and reporting of results.” Scientific rigor also includes transparency in reporting full experimental details so that others may reproduce experimental procedures and extend the findings.

The MMRRC helps you address the NIH’s new focus areas of rigor and transparency:

  • Scientific Premise – the MMRRC provides genetically-engineered mouse models for virtually every field of biomedical research ranging from neurobiology to infectious disease. These mouse models are critical to the advancement of our understanding of health and disease.
  • Rigorous Experimental Design – the MMRRC provides authentic and key biological resources that are easily reported and described using unique identifiers (e.g., RRID numbers) to ensure full transparency so that others may obtain the same models with which to reproduce studies.
  • Consideration of Relevant Biological Variables – models from the MMRRC are genetically defined (including background strain genetics, incipient congenic strains and congenic strains) and confirmed specific-pathogen–free. Moreover, the MMRRC has extensive expertise in troubleshooting how other biological variables, such as husbandry factors, microbiota and sex, may modulate phenotypes. By obtaining mice from the MMRRC you eliminate the risk of genetic drift or contamination with adventitious pathogens that potentially can arise through the use of long standing in-house colonies or obtaining mice from colleagues. Furthermore, mice obtained through the MMRRC minimizes interlab variability and negates the need for extensive regenotyping and phenotyping. In addition, the MMRRC supports the NC3R’s ARRIVE (Animal Research: Reporting of In Vivo Experiments) initiative to improve the reporting of research using animals. The MMRRC centers’ stand behind and support efforts with 3R development, training and advances and as such adheres to standardized reporting guidelines.
Career Development Assistance

In addition to a commitment to reproducibility, the MMRRC provides training opportunities in research using genetically-altered mice. We believe in fostering the development of outstanding scientists and to help them expand their potential to make significant contributions in their field of research. The MMRRC has the ability to provide training through guest lectures, webinars, seminars, and workshops in areas including nomenclature and biological variables to name just a few.

If you are interested in learning more about educational training and career development please contact service@mmrrc.org directly to find out how MMRRC can assist you with your educational needs.

Authentication of Mice Using the Strain Detail Sheet

At the MMRRC we document, verify and authenticate each detail on our archived strains. Investigators wishing to publicize information about their strains on their own web site may want to include a link to the MMRRC's Strain Detail Sheet (SDS) for their specific strain. This would save visiting investigators from having to locate it themselves. On the SDS page, investigators will find information provided by the donating investigator, additional information curated by the MMRRC, relevant genotyping protocols and specifics about husbandry, care, and management. In addition, users can find information on availability and prices, including fees for shipping and handling, for available product items. The online request form can be accessed directly from a strain’s SDS page.

How to Acknowledge MMRRC Mice

Your research is important to the MMRRC and the greater research community. By obtaining mice from the MMRRC, we respectfully request that you acknowledge the MMRRC (Mutant Mouse Resource and Research Center) in your research publications. Suggested text is to include in publications, grants, and presentations is provided below. As an NIH-supported, not-for-profit resource center, your acknowledgement is vital to inform others of our commitment to rigor, transparency and reproducibility. We ask that investigators provide via email (service@mmrrc.org) copies of any published papers using products obtained from the MMRRC.

The significance of understanding and documenting the genetic backgrounds of mouse models used in research is of utmost importance for the Mutant Mouse Resource & Research Center (MMRRC). The MMRRC understands that if research is to be reliable and reproducible, specific quality control measures and testing need to be in place. Models available from the MMRRC repository have well documented defined, stable genetic backgrounds. This strong genetic integrity coupled with quality control measures allows investigators to generate robust and reproducible results for future comparison.

In help ensure that MMRRC strains are held to the highest standards to optimize reproducibility of studies, all submitted strains are thoroughly reviewed and documented and include additional quality control measures that involve:

  • Critical assessment of incoming strains – all submissions require detailed information about method of genetic manipulation, genotype and genotyping procedures, genetic background (e.g. source of strain and ES cell used in development, number of background generations and backcross parent strain), and reproducible phenotype.
  • Thorough strain description – for each strain, a strain detail sheet (SDS) is created that includes strain name using established nomenclature guidelines, gene details, strain description, research applications, strain origin and colony and husbandry information. Moreover, the primary reference(s) for the strain are available through PMCID or PMID links, and the MMRRC maintains contact with the submitting investigator to aid in troubleshooting phenotype reproducibility. Phenotype information that arises in the literature from use of these strains is added on a regular basis.
  • The genetic identity of all strains is confirmed upon receipt of donated animals and prior to shipment of animals/materials to requesting investigators. Genotyping assays are optimized and standardized protocols are available to ensure that investigators have a means to genotype any MMRRC strains they receive and maintain.
  • To provide additional genetic information for congenic strains, background strain information can be ascertained using MegaMUGA, a low-cost high-density genotyping platform. This may be especially critical to investigations using incipient congenic strains (between N5 and N10) that are not fully congenic. Many MMRRC strains including the highest demand strains already have this information provided.
  • MMRRC strains are maintained with strict biosecurity SOPs and rigorous health monitoring programs with extensive exclusion lists that include all known pathogens of mice and the vast majority of opportunists. Health monitoring tests use state-of-the art methodology and the MMRRC can test for agents not on its exclusion list.
  • Detailed descriptions of MMRRC facilities and husbandry conditions (housing, diet, bedding, etc.) are provided.
  • The MMRRC Conditions of Use agreement encourages procurement of animals directly from the MMRRC in an effort to ensure rigorous genetic and biosecurity control of strains. This can avoid issues of genetic contamination, misidentification of strains, and changes in animal health that can occur at independent institutions.
  • The MMRRC provides numerous value-added services that can aid investigators in troubleshooting phenotype deviations and ensuring reproducibility. These include, but are not limited to, genotyping, karyotyping, speed congenics, health monitoring, microbiome analyses, and an array of phenotyping assays.
  • MMRRC scientists and veterinarians are readily available for consultation about use of MMRRC strains.