Over 600,000 people in the U.S. suffer from kidney diseases; more than 50,000 die each year. Mouse models are the paradigm for characterizing the etiology and pathogenesis of kidney diseases. The purpose of this project is to identify the mutated genes in two novel mouse models for kidney disease. Bilateral polycystic kidneys (bpck) is a spontaneous recessive mutation that causes classic polycystic kidney disease. It is a new model because it maps to a region of the mouse genome that has no other kidney disease gene. Based on conserved homology, bpck will likely indicate a new human polycystic kidney disease gene. Variable hydronephrosis (vhn) is a recessive mutation caused by one of the breakpoints of a reciprocal translocation. vhn presents uni- or bilateral hydronephrosis and renal agenesis/dysgenesis. Preliminary genetic analyses indicate that each of the phenotypes is caused by mutation in a single major gene.
Aim 1 is to refine the chromosomal positions of the mutations with a high resolution genetic intercross for bpck and BAC/FISH physical mapping for vhn.
Aim 2 is to identify the mutated genes using the positional candidate gene approach and standard molecular protocols. Human orthologues and gene locations will be predicted from the results.
Aim 3 is to analyze in detail the disease phenotypes and progression. Gene expression patterns will be determined by TISH and protein localization by immunochemistry.
Aim 4 is to analyze gene function by identifying interacting genes using microarrays and quantitative RT-PCR.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Mammalian Genetics Study Section (MGN)
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Rasooly, Rebekah S
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Jackson Laboratory
Bar Harbor
United States
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Davisson, Muriel T; Cook, Susan A; Akeson, Ellen C et al. (2015) Kidney adysplasia and variable hydronephrosis, a new mutation affecting the odd-skipped related 1 gene in the mouse, causes variable defects in kidney development and hydronephrosis. Am J Physiol Renal Physiol 308:F1335-42
Korstanje, Ron; Caputo, Christina R; Doty, Rosalinda A et al. (2014) A mouse Col4a4 mutation causing Alport glomerulosclerosis with abnormal collagen ?3?4?5(IV) trimers. Kidney Int 85:1461-8
Davisson, Muriel T; Bergstrom, David E; Reinholdt, Laura G et al. (2012) Discovery Genetics - The History and Future of Spontaneous Mutation Research. Curr Protoc Mouse Biol 2:103-118
Cook, Susan A; Collin, Gayle B; Bronson, Roderick T et al. (2009) A mouse model for Meckel syndrome type 3. J Am Soc Nephrol 20:753-64