Many common inherited human diseases are genetically complex;that is, they result from the interaction of more than one gene. Examples are diabetes, cardiovascular diseases, cancer, obesity, asthma, and susceptibility to infectious disease. Even genetically """"""""simple"""""""" single mutation diseases are frequently modulated in severity by secondary genes. The advances in positional candidate gene analysis have led to relatively rapid identification of the genes underlying many human and mouse disorders caused by single gene mutations. Similarly, the goal of genetic analysis of genetically complex diseases is to discover the underlying genes with the ultimate goal of prevention or therapy. Genetic analysis of complex traits requires model systems in which genetic manipulations can be carried out. The metabolic, organ/tissue, and genetic similarities between mice and humans and the ease with which the mouse can be genetically manipulated make mice the obvious model for many of these complex human diseases. Linkage crosses for complex trait analysis, however, are time-consuming and expensive because of the large number of mice required. The Special Mouse Strains Resource (SMSR) funded by this grant maintains and distributes strain panels that are valuable tools for efficient complex trait analysis and whose use will improve the efficiency of identifying genes in mouse models of human polygenic diseases. The SMSR contains five Recombinant Inbred (Rl) strain panels and a set of 21 Consomic or Chromosome Substitution (CS) strains totaling 110 individual strains. We propose in this amended renewal to add a second CS panel - C57BL/6J-Chr #PWD - of 26 strains and 46 additional BXD Rl strains.
The specific aims of this grant are to (1) maintain and distribute the existing s110 strains, including develop a panel of SNPs for genetic monitoring of all SMSR strains;(2) add two new strains sets (above);(3) carry out research to enhance the value of the strains - (a) characterize selected phenotypes, including immunology, hematology, clinical chemistry, lung function, bone density, body composition, behavior, hearing and vision, and (b) collect reproductive data on all strains maintained;and (4) provide all data generated to the scientific public via the Mouse Phenome Database and the JAX web site. Because mice and human beings get the same genetically complex diseases, identifying the genetic basis for these complex diseases in mice will lead to preventive and therapeutic treatments in human patients for diseases such as heart disease, diabetes, obesity, asthma, and susceptibility to infectious diseases.
| Livraghi-Butrico, Alessandra; Grubb, Barbara R; Kelly, Elizabeth J et al. (2012) Genetically determined heterogeneity of lung disease in a mouse model of airway mucus obstruction. Physiol Genomics 44:470-84 |
| Govoni, K E; Donahue, L R; Marden, C et al. (2008) Complex genetic regulation of bone mineral density and insulin-like growth factor-I in C57BL/6J-Chr #A/J/NaJ chromosome substitution strains. Physiol Genomics 35:159-64 |
| Davisson, Muriel T; Taft, Robert A (2006) Strategies for managing an ever increasing mutant mouse repository. Brain Res 1091:255-7 |
