Researchers across the State of Tennessee have combined their expertise in ENU mutagenesis of the mouse genome and neurosciences to conduct a concerted effort to mutagenize the mouse genome, screen for deficits in neural function and structure, and thereby lay the basis for a large scale analysis of the functional genomics of the nervous system. A novel mutagenesis program is employed whereby markers (coat color or molecular/PCR-based) identify mice (test class) that potentially carry mutations in specific chromosomal regions. This approach serves as a strong foundation for the genetic dissection of phenotype and genotype relationships in brain by offering an economy of effort and reliability in addition to pre-localizing mutations to discrete regions of the genome. A profile of neural function is obtained from all potentially mutant mice by high throughput screens that examine basic behavior, gross structure, and histology of the nervous system. Four domains (alcohol, drugs of abuse, eye, and social behavior) will phenotype mature mice from each pedigree. A fifth domain (aging) will focus on late onset phenotypic abnormalities of nervous system function and structure. The use of markers to identify test class animals permits the efficient aging of all pedigrees. Animals that are flagged by demonstrating aberrant results in a primary screen will be moved into secondary screens that characterizes the molecular phenotype of the brain and eye as well as explore performance in the domains of learning and memory, audition, and nociception. The BioInformatics Core tracks all mice, collects and stores the phenotypic data on each, mouse, flags mice with aberrant phenotypes, and provides a means for investigators (both inside and outside the consortium) to access and analyze this data. A Research Community Core will work with out veterinarians to promote the use of our mutant mice by outside researchers. An external advisory panel assists in this effort as well as in the design of additional phenotypic screens.
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