The number of genetically modified mouse strains has expanded greatly in recent years, resulting in increased pressure to preserve and make these mice available for research. In March 1998, the National Institutes of Health (NIH) held a meeting on "Priority Setting for Mouse Genomics and Genetics Resources."

In response to this need and the meeting recommendations, NIH & DHHS established the Mutant Mouse Resource & Research Centers (MMRRC) to serve the scientific community. The MMRRC was started in 1999 with funding through cooperative research agreements (U42) that involve development of animal model resources.

The MMRRC was initiated by NCRR in 1999 with the awarding of five grants. In May 2001, the MMRRC launched its public website and began accepting applications for submissions of strains to the repository. In October 2002, the MMRRC's first strains became available to requesting investigators.

In 2002, the MMRRC greatly expanded the resource by adding mouse ES cell lines for distribution, starting with the gene trap clones created by the NIH/NHLBI-sponsored BayGenomics PGA program. Additional cell line collections have been added since. Over 15,000 ES cell lines are available now, with more ES cell lines becoming available over the coming years. The MMRRC distributes ES cell lines, as well as mice derived from them.

During 2005, the MMRRC became one of the founding members of the Federation of International Mouse Resources (FIMRe) working to enhance the world-wide availability of mouse research resources.