application) Chronic renal failure frequently progresses to end stage renal disease (ESRD), resulting in significant morbidity, mortality and economic burden to the health care delivery system. The lack of effective therapies for chronic renal failure is partly a testament to the complex nature of the disease. Accumulating evidence suggests that genetic predisposition plays important role in the progression of chronic renal failure to ESRD. To date, no nephropathy susceptibility gene(s) have yet been identified in humans, despite the efforts of multiple laboratories using classical genetic methods, including gene mapping and loci scanning. We propose to utilize an animal model for ESRD (the oligosyndactyly mouse) to try to identify genes that might be involved in the pathogenesis and/or affect the progression of chronic renal failure to ESRD. We adopted an empiric approach utilizing a novel powerful technique called serial analysis of gene expression (SAGE) that will allow systematic analysis and comparison of gene expression libraries in diseased animals and their wild type controls.
Our Specific Aims are: 1) To generate SAGE expression libraries from kidneys of ROP-Os/+, C57BL/6-Os/+, ROP-+/+, and C57BL/6-+/+ mice, and 2) To analyze the expression libraries using Monte Carlo simulation analysis and hierarchical clustering to identify candidate genes and pathways involved in renal disease pathogenesis. An algorithm is proposed to prioritize candidate genes identified by these analyses of the libraries. Functional analysis of these genes will be performed in future studies using standard molecular and genetic techniques, which will allow us to learn more about pathways critical for renal disease pathogenesis. Ultimately, this might pave the way to the development of new therapeutic and/or diagnostic modalities.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08DK002699-03
Application #
6524110
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Rankin, Tracy L
Project Start
2000-09-30
Project End
2005-08-31
Budget Start
2002-09-01
Budget End
2003-08-31
Support Year
3
Fiscal Year
2002
Total Cost
$123,430
Indirect Cost
Name
Case Western Reserve University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
El-Meanawy, Ashraf; Schelling, Jeffery R; Iyengar, Sudha K et al. (2012) Identification of nephropathy candidate genes by comparing sclerosis-prone and sclerosis-resistant mouse strain kidney transcriptomes. BMC Nephrol 13:61
Schelling, Jeffrey R; El-Meanawy, M Ashraf; Barathan, Shrinath et al. (2002) Generation of kidney transcriptomes using serial analysis of gene expression. Exp Nephrol 10:82-92
Schelling, Jeffery R; Sinha, Sumita; Konieczkowski, Martha et al. (2002) Myofibroblast differentiation: plasma membrane microdomains and cell phenotype. Exp Nephrol 10:313-9