Inducible gene silencing in podocytes: A new tool for studying glomerular function

Laurence Bugeon, Aliki Danou, David Carpentier, Paul Langridge, Nelofer Syed, Margaret J. Dallman

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Glomerular filtration is one of the primary functions of the kidney. Podocytes, a highly specialized cell type found in glomeruli, are believed to play a critical role in that function. Null mutations of genes expressed in podocytes like WT1, nephrin, and NEPH1 result in an embryo and perinatal lethal phenotype and therefore do not allow the functional analysis of these genes in the adult kidney. Here is describes the generation of a model that will allow such studies. We have engineered transgenic mice in which the disruption of targeted genes can be induced in a temporally controlled fashion in podocytes. For this, a transgene encoding the mutated estrogen receptor-Cre recombinase fusion protein was introduced into the mouse genome. Animals were crossed with Z/AP reporter mice to test for efficient and inducible recombination. We found that, after injection of inducer drug tamoxifen, Cre fusion protein translocates to the nuclei of podocytes, where it becomes active and mediates recombination of DNA carrying loxP target sequences. These animals provide for the first time a tool for silencing genes selectively in podocytes of adult animals.

Original languageEnglish (US)
Pages (from-to)786-791
Number of pages6
JournalJournal of the American Society of Nephrology
Volume14
Issue number3
DOIs
StatePublished - Mar 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Nephrology

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