Kidney disease is a major economic and health burden in the United States. Several studies, in human , rat, and mouse, have established a genetic component to kidney disease;however, relatively few causal genes have been identified and the current animal models for the study of kidney disease are insufficient . Mutagenesis is an effective method for identifying disease-causing genes in mice and establishing novel murine models of disease. We propose to screen mutagenized mice from the Heart, Lung, and Blood Mutagenesis Program at The Jackson Laboratory for mutations leading to kidney disease. We will screen third generation progeny , enabling us to detect both dominant and recessive mutations . Based on our successful pilot study, we expect to screen 4500 mutagenized mice to identify 45 phenotypic deviants, and we anticipate that 15-20 of these will transmit heritable mutations. For each new mutant strain, we will map the causal mutation to a chromosomal position, characterize renal structure and function , and establish a colony for distribution to the research community. Additionally , we will make substantial progress towards cloning the causal mutation in at least two of the mutant strains. Completion of the proposed aims will provide the research community with new, well-characterized animal models of kidney disease. The proposed research will advance our knowledge of the genetics of kidney disease in the short term by identifying causal genes and provide valuable resources for the continued study of kidney disease in animal models over the long- term.
