Abstract

This is the second renewal application for this project to understand the role of genetic changes in the pathogenesis of glomerular diseases like focal segmental glomerulosclerosis (FSGS). In this application, we propose two specific aims. In the first, we propose to characterize a gene that we discovered that is highly expressed in podocytes. This gene, ARHGAP24, is a known regulator of the actin cytoskeleton and the high expression of this gene implicates a specific actin regulatory pathway in the normal function of podocytes. To test the role of this gene in the glomerulus, we propose to generate and characterize a mouse that lacks expression of ARHGAP24. In the second aim, we will set-up a genetic screen that combines RNAi technology and state of the art mouse genetic methods to perform a genetic screen in mouse to identify genes that when mutated contribute with CD2AP and another podocyte specific gene, synaptopodin, in the pathogenesis of glomerular dysfunction. Our long-term goal is the identification of all genes that, when mutated, contribute to the pathogenesis of human FSGS.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK058366-14
Application #
8516016
Study Section
Pathobiology of Kidney Disease Study Section (PBKD)
Program Officer
Mullins, Christopher V
Project Start
2000-09-15
Project End
2015-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
14
Fiscal Year
2013
Total Cost
$261,852
Indirect Cost
$63,617

  Institution

Name
Washington University
Department
Pathology
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130

  Publications

Funk, Steven D; Lin, Meei-Hua; Miner, Jeffrey H (2018) Alport syndrome and Pierson syndrome: Diseases of the glomerular basement membrane. Matrix Biol 71-72:250-261
Fissell, William H; Miner, Jeffrey H (2018) What Is the Glomerular Ultrafiltration Barrier? J Am Soc Nephrol 29:2262-2264
Germino, Elizabeth A; Miller, Joseph P; Diehl, Lauri et al. (2018) Homozygous KSR1 deletion attenuates morbidity but does not prevent tumor development in a mouse model of RAS-driven pancreatic cancer. PLoS One 13:e0194998
Luo, Wentian; Olaru, Florina; Miner, Jeffrey H et al. (2018) Alternative Pathway Is Essential for Glomerular Complement Activation and Proteinuria in a Mouse Model of Membranous Nephropathy. Front Immunol 9:1433
Brähler, Sebastian; Zinselmeyer, Bernd H; Raju, Saravanan et al. (2018) Opposing Roles of Dendritic Cell Subsets in Experimental GN. J Am Soc Nephrol 29:138-154
Eng, Diana G; Kaverina, Natalya V; Schneider, Remington R S et al. (2018) Detection of renin lineage cell transdifferentiation to podocytes in the kidney glomerulus with dual lineage tracing. Kidney Int 93:1240-1246
Bartlett, Christina S; Scott, Rizaldy P; Carota, Isabel Anna et al. (2017) Glomerular mesangial cell recruitment and function require the co-receptor neuropilin-1. Am J Physiol Renal Physiol 313:F1232-F1242
Suleiman, Hani Y; Roth, Robyn; Jain, Sanjay et al. (2017) Injury-induced actin cytoskeleton reorganization in podocytes revealed by super-resolution microscopy. JCI Insight 2:
Beckerman, Pazit; Bi-Karchin, Jing; Park, Ae Seo Deok et al. (2017) Transgenic expression of human APOL1 risk variants in podocytes induces kidney disease in mice. Nat Med 23:429-438
Tsuji, Kenji; Suleiman, Hani; Miner, Jeffrey H et al. (2017) Ultrastructural Characterization of the Glomerulopathy in Alport Mice by Helium Ion Scanning Microscopy (HIM). Sci Rep 7:11696

Showing the most recent 10 out of 31 publications