The mission of the Mouse Mutant Resource (MMR) at The Jackson Laboratory (JAX) is to provide mouse models for biomedical and biological research. Spontaneous mutations continue to be a major source of mouse models for human disorders. They complement specifically targeted mutations and have the advantage that they are first recognized by biomedically-relevant phenotypes and do not require prior knowledge of the underlying genes. The specific objectives of the MMR program are to 1) identify the causative genetic mutation in spontaneous mutant strains with heritable phenotypes using SNP-based mapping and high throughput sequencing (HTPS);2) characterize new mutants phenotypically by defining their anatomical, histopathological, physiological, and ultrastructural abnormalities;3) provide resources to the scientific community by publishing information on new mutants, preserving them as frozen gametes or embryos and DNA for future molecular analysis, and distributing mice to other investigators, and 4) enhance the identification rate of causative mutations using comparative genome hybridization, RNASeq and improved bioinformatics analysis methods for HTPS. New mutants are discovered as pljienotypic deviants appearing in JAX's large breeding colonies and characterized genetically by determining mode of inheritance, testing for allelism with known mutations that produce similar phenotypes, determining chromosomal locations and identifying the mutated gene using exome or whole genome sequencing. Each new mutant is characterized phenotypically by observing its growth, viability, fertility, life span and behavior and by defining its anatomical, histopathological and physiological abnormalities. For those mutants with phenotypes that model human disorders, deeper phenotyping is carried out to enhance their value. The MMR team has expertise in bone biology, reproduction, general histopathology and neuropathology;we collaborate with experienced investigators in other fields including hearing, vision and metabolomics. All new mutants are published in peer-reviewed journals or presented on the MMR and JAX web sites, and related information is made available through the Mouse Genome Database.
The research in this project will provide new mouse models for specific human disorders and for basic biomedical research to understand biological systems implicated in human diseases. Mouse models enable scientists to understand the causes and pathologies of similar human diseases so that prevention strategies or therapeutics for these diseases can be developed. In addition, mouse models play a critical role in testing therapies or drugs prior to human trials to assess efficacy and safety.
|Chang, Bo (2016) Mouse Models as Tools to Identify Genetic Pathways for Retinal Degeneration, as Exemplified by Leber's Congenital Amaurosis. Methods Mol Biol 1438:417-30|
|Pratt, C Herbert; Dionne, Louise A; Fairfield, Heather et al. (2016) Gnaq(M1J): An ENU-Induced Mutant Allele Affecting Pigmentation in the Mouse. J Invest Dermatol 136:334-6|
|Asinof, Samuel; Mahaffey, Connie; Beyer, Barbara et al. (2016) Dynamin 1 isoform roles in a mouse model of severe childhood epileptic encephalopathy. Neurobiol Dis 95:1-11|
|Jones, Julie M; Dionne, Louise; Dell'Orco, James et al. (2016) Single amino acid deletion in transmembrane segment D4S6 of sodium channel Scn8a (Nav1.6) in a mouse mutant with a chronic movement disorder. Neurobiol Dis 89:36-45|
|Herbert Pratt, C; Potter, Christopher S; Fairfield, Heather et al. (2015) Dsp rul: a spontaneous mouse mutation in desmoplakin as a model of Carvajal-Huerta syndrome. Exp Mol Pathol 98:164-72|
|Fairfield, Heather; Srivastava, Anuj; Ananda, Guruprasad et al. (2015) Exome sequencing reveals pathogenic mutations in 91 strains of mice with Mendelian disorders. Genome Res 25:948-57|
|Liu, Ye; Lee, Jeong Woong; Ackerman, Susan L (2015) Mutations in the microtubule-associated protein 1A (Map1a) gene cause Purkinje cell degeneration. J Neurosci 35:4587-98|
|Pratt, C Herbert; Dionne, Louise; Fairfield, Heather et al. (2015) Gnaq(M1J): An ENU Induced Mutant Allele Affecting Pigmentation in the Mouse. J Invest Dermatol :|
|Li, Qiaoli; Pratt, C Herbert; Dionne, Louise A et al. (2014) Spontaneous asj-2J mutant mouse as a model for generalized arterial calcification of infancy: a large deletion/insertion mutation in the Enpp1 gene. PLoS One 9:e113542|
|Johnson, Kenneth R; Gagnon, Leona H; Longo-Guess, Chantal M et al. (2014) Hearing impairment in hypothyroid dwarf mice caused by mutations of the thyroid peroxidase gene. J Assoc Res Otolaryngol 15:45-55|
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