FSGS: Animal Models and Novel Biomarkers

Cincinnati Childrens Hosp Med Ctr, Cincinnati OH

Investigators

Linked publications, trials & patents

Abstract

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).