Normal kidney development in humans is the result of a complex pathway that is poorly understood at the molecular level. Mice with mutations affecting kidney development offer excellent resources for identifying critical genes in this pathway, and have all the experimental advantages that the mouse system offers. Mouse Urogenital Syndrome is an autosomal recessive disorder that primarily involves defects of the urogenital and skeletal systems. These defects can include small, cystic kidneys, other defects of the urogenital system, missing and malformed ribs and vertebrae, mild neurological symptoms, and a coat texture defect. The primary goal of this project is to clone the gene for mouse Urogenital Syndrome (US). This will be accomplished by breeding additional interspecific backcross mice for linkage analysis to reduce the size of the candidate region. YAC contig generation and physical mapping around the US locus will accompany reduction of the candidate region. Candidate genes in this minimal region will be identified by exon trapping and/or cDNA isolation. DNA and RNA from affected and unaffected animals will be examined for alterations in these candidates. Based on linkage analysis, the Rxra gene has been identified as a candidate for US. The Rxra gene has been examined by Southern analysis, northern analysis, and partial sequencing of RT-PCR products from mRNA, and to date, no alterations have been found. ultimately, the US gene will be definitively identified by introduction into transgenic animals and """"""""curing"""""""" the defect. It is hoped that the isolation of this critical gene will serve as the cornerstone of a program enabling better understanding of kidney development by identification of disease-causing genes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29DK051024-05
Application #
2905842
Study Section
General Medicine B Study Section (GMB)
Project Start
1995-09-01
Project End
2000-08-31
Budget Start
1999-09-01
Budget End
2000-08-31
Support Year
5
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Eleanor Roosevelt Institute for Cancer Research
Department
Type
DUNS #
City
Denver
State
CO
Country
United States
Zip Code
80206