Focal Segmental Glomerulosclerosis (FSGS) represents the most common cause of acquired kidney failure in children and the frequency is increasing. The causes of FSGS remain largely unknown. There are several known genetic causes of FSGS. Mouse models with mutations in these same genes associated with FSGS in humans have been generated that show a very pronounced FSGS-like disease. We propose to derive a deeper understanding of the molecular pathways of pathogenesis of mutation-based FSGS by making use of the genetic power of the mouse coupled with the global gene expression analysis power of RNA-Seq/ microarrays, as outlined below:
Specific aim 1. We propose a RNA-Seq/microarray dissection of pathogenic pathways in each major cell type of the glomerulus in Actn4 mutant mice.
Specific aim 2. We propose a similar molecular dissection of the altered gene expression programs of each glomerular cell type in a bigenic mouse model of FSGS. ! Specific aim 3. As a complement to aims 1 and 2 we propose a proteomics analysis of the glomeruli of the FSGS model Actn4 and Cd2ap/Fyn mutant mice. This project will involve a multidisciplinary team of basic, translational and clinical investigators, and will prominently require the services of at least two of the proposed Center's Cores, namely the Gene Expression Core (Core A) and the Protomics Core (Core B).

Public Health Relevance

Focal Segmental Glomerulosclerosis (FSGS) represents the most common cause of acquired kidney failure in children and contributes to an enormous major impact on the U.S. public health and a major financial burden. Project 2 of this Center of Excellence will utilize multiple investigators and multiple Center Cores to provide critical results of studies aimed at understanding the causes of this dismal disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Specialized Center (P50)
Project #
1P50DK096418-01
Application #
8397986
Study Section
Special Emphasis Panel (ZDK1-GRB-G (M3))
Project Start
Project End
Budget Start
2012-09-21
Budget End
2013-08-31
Support Year
1
Fiscal Year
2012
Total Cost
$87,268
Indirect Cost
$30,230
Name
Cincinnati Children's Hospital Medical Center
Department
Type
DUNS #
071284913
City
Cincinnati
State
OH
Country
United States
Zip Code
45229
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