About the Resource
Where strains originate
New spontaneous mutants arise rarely, but continually within the large colonies at the Jackson Laboratory during the course of breeding. Upon discovery these mutants are isolated and screened for inclusion in the Mouse Mutant Resource collection, protecting the genetic integrity of the parental strain while providing new mutant strains for characterization. Strains may also be acquired from the research colonies of principal investigators at The Jackson Laboratory and from external investigators who wish to donate spontaneous mutant strains to the resource. In addition to spontaneously arising strains, the Mouse Mutant Resource occasionally accepts mutant strains developed through ENU (or other) mutagenesis programs.
Why study spontaneous mutations?
Many aspects of human health and disease involve complex processes that can only be studied in the context of a living organism. Mice harboring spontaneous mutations have long been a major source for animal models of human genetic disorders, and recent technological advances make the molecular identification of disease-causative mutations faster and more precise than ever. Spontaneous mouse mutations offer many advantages over engineered mutations in understanding human genetic disorders and basic gene function, including:
- Phenotype-driven mutations provide insight into the function and biomedical relevance of the mutant gene. Starting with a known phenotype avoids effort spent on producing less predictable engineered mutations that may cause embryonic lethality or lack phenotypes altogether.
- Multiple strain backgrounds reveal modifying genes, pathways and interactions. Spontaneous mutations arise on a wide variety of strain backgrounds. This variation enables the discovery of disease-modifying genes and can be essential to the discovery of important mutant phenotypes that may not manifest on the few strains used for genetically engineered mutations.
- Allelic series — the initial mutant allele plus all subsequent alleles occurring within a given gene — are important for elucidating domain-specific protein functions and transcript-specific mRNA functions that cannot be modeled by genetically engineered null alleles.
- Spontaneous mutations offer an unbiased system for new gene
discoveries with a diversity of mutation types. Because they occur naturally, spontaneous mutations produce a full and unbiased array of mutation types that may better model human disease-causing genomic variation. Spontaneous mutations also cause varying effects on transcript/gene expression and protein function in addition to the complete loss of function effects that are generally produced by genetically engineered disruptions.
How MMR strains are used in research
Within just the last five years these important mouse models have been distributed to over 1,400 investigators at more than 350 institutions. Moreover, since 2007, MMR mice carrying a characterized spontaneous mutations have contributed to over 1,500 peer-reviewed publications.
