Podocyte-specific expression of Cre recombinase promotes glomerular basement membrane thickening

American Journal of Physiology. Renal Physiology
Rohan S BalkawadeCaroline B Marshall

Abstract

Conditional gene targeting using Cre recombinase has offered a powerful tool to modify gene function precisely in defined cells/tissues and at specific times. However, in mammalian cells, Cre recombinase can be genotoxic. The importance of including Cre-expressing control mice to avoid misinterpretation and to maximize the validity of the experimental results has been increasingly recognized. While studying the role of podocytes in the pathogenesis of glomerular basement membrane (GBM) thickening, we used Cre recombinase driven by the podocyte-specific podocin promoter (NPHS2-Cre) to generate a conditional knockout. By conventional structural and functional measures (histology by periodic acid-Schiff staining, albuminuria, and plasma creatinine), we did not detect significant differences between NPHS2-Cre transgenic and wild-type control mice. However, surprisingly, the group that expressed Cre transgene alone developed signs of podocyte toxicity, including marked GBM thickening, loss of normal foot process morphology, and reduced Wilms tumor 1 expression. GBM thickening was characterized by altered expression of core structural protein laminin isoform α5β2γ1. RNA sequencing analysis of extracted glomeruli identified 230 genes ...Continue Reading

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Citations

Apr 4, 2019·American Journal of Physiology. Renal Physiology·Leslie S Gewin
Feb 23, 2020·Cell Death & Disease·Julie K BrayThomas D Schmittgen
Jan 8, 2020·Antioxidants & Redox Signaling·Elisa B RandiDavid Hoogewijs
Jun 10, 2020·Lab Animal·Michelle N PerryCynthia L Smith
Oct 8, 2019·American Journal of Physiology. Renal Physiology·Madeleine FrahsekMarcus J Moeller
Mar 30, 2021·American Journal of Physiology. Renal Physiology·Lisa M CurtisAnupam Agarwal
Oct 31, 2021·Journal of the American Society of Nephrology : JASN·Janina Müller-DeileMario Schiffer

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Methods Mentioned

BETA
transgenic
chromosomal aberration
gene knockout
biopsies
Genotyping
PCR
ELISA
Flow Cytometry
electrophoresis
targeted mutation

Software Mentioned

Protein Analysis Through Evolutionary Relationships ( PANTHER )
Database for Annotation , Visualization , and Integrated Disco...
PANTHER
DAVID
GraphPad
Adobe Photoshop
ImageJ
GraphPad Prism
Cuffdiff
Velocity

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