Referenced in: none

Automatically associated channels: TRP , TRPC , TRPC6

Title: Podocyte-specific overexpression of wild type or mutant trpc6 in mice is sufficient to cause glomerular disease.

Authors: Paola Krall, Cesar P Canales, Pamela Kairath, Paulina Carmona-Mora, Jessica Molina, J Daniel Carpio, Phillip Ruiz, Sergio A Mezzano, Jing Li, Changli Wei, Jochen Reiser, Juan I Young, Katherina Walz

Journal, date & volume: PLoS ONE, 2010 , 5, e12859

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20877463

Abstract
Mutations in the TRPC6 calcium channel (Transient receptor potential channel 6) gene have been associated with familiar forms of Focal and Segmental Glomerulosclerosis (FSGS) affecting children and adults. In addition, acquired glomerular diseases are associated with increased expression levels of TRPC6. However, the exact role of TRPC6 in the pathogenesis of FSGS remains to be elucidated. In this work we describe the generation and phenotypic characterization of three different transgenic mouse lines with podocyte-specific overexpression of the wild type or any of two mutant forms of Trpc6 (P111Q and E896K) previously related to FSGS. Consistent with the human phenotype a non-nephrotic range of albuminuria was detectable in almost all transgenic lines. The histological analysis demonstrated that the transgenic mice developed a kidney disease similar to human FSGS. Differences of 2-3 folds in the presence of glomerular lesions were found between the non transgenic and transgenic mice expressing Trpc6 in its wild type or mutant forms specifically in podocytes. Electron microscopy of glomerulus from transgenic mice showed extensive podocyte foot process effacement. We conclude that overexpression of Trpc6 (wild type or mutated) in podocytes is sufficient to cause a kidney disease consistent with FSGS. Our results contribute to reinforce the central role of podocytes in the etiology of FSGS. These mice constitute an important new model in which to study future therapies and outcomes of this complex disease.