International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)


C Bult
The Jackson Laboratory

Frankel W, Seburn K, Peters L, Svenson K, O’Brien T
The Jackson Laboratory

Gene-based approaches for exploring function and phenotype in the laboratory mouse are powerful and efficient but are not sufficient due to the complexity and redundancy of biological processes in mammalian systems. Phenotype driven approaches to understanding biological complexity are complementary to gene-driven approaches but suffer from a reliance on the availability of appropriate mutations, leaving a significant gap between the universe of possible phenotypes and those that are available for study. The Jackson Laboratory (TJL) has established two large-scale mutagenesis centers to generate new mouse models for human disease and to close the “phenotype gap.” The TJL Neuroscience Mutagenesis Facility seeks to produce new mouse models of human neurological disease. The TJL Mouse Heart, Lung, Blood, and Sleep Disorders Center links quantitative trait loci (QTL) and single-gene mutations to gene function and disease and seeks to dissect the genetic variation underlying complex cardiovascular, lung, hematopoietic, and sleep dysfunction.Both mutagenesis centers at The Jackson Laboratory generate new mutations using ethyl nitro-sourea (ENU) in both genome-wide and specific genomic region screens using normal C57BL/6J mice and sensitized mutant mice. This classic strategy is being complemented by implementation of new mutagenesis technologies utilizing embryonic stem cells and other mutagens to increase efficiency. Following mutagenesis, mice are screened for recessive mutations in the relevant biological domain using a series of comprehensive phenotype screens The goal of each center is to screen approximately 4-5,000 third generation mutagenized mice and to identify 50 new mouse models in their respective domains each year.

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