Loss of NFAT5 results in renal atrophy and lack of tonicity-responsive gene expression

Cristina López-Rodríguez, Christopher L. Antos, John M. Shelton, James A. Richardson, Fangming Lin, Tatiana I. Novobrantseva, Roderick T. Bronson, Peter Igarashi, Anjana Rao, Eric N. Olson

Research output: Contribution to journalArticlepeer-review

233 Scopus citations


The transcription factor NFAT5/TonEBP, a member of the NFAT/Rel family of transcription factors, has been implicated in diverse cellular responses, including the response to osmotic stress, integrin-dependent cell migration, T cell activation, and the Ras pathway in Drosophila. To clarify the in vivo role of NFAT5, we generated NFAT5-null mice. Homozygous mutants were genetically underrepresented after embryonic day 14.5. Surviving mice manifested a progressive and profound atrophy of the kidney medulla with impaired activation of several osmoprotective genes, including those encoding alclose reductase, Na+/CI--coupled betaine/γ-aminobutyric acid transporter, and the Na+/myo-inositol cotransporter. The aldose reductase gene is controlled by a tonicity-responsive enhancer, which was refractory to hypertonic stress in fibroblasts lacking NFAT5, establishing this enhancer as a direct transcriptional target of NFAT5. Our findings demonstrate a central role for NFAT5 as a tonicity-responsive transcription factor required for kidney homeostasis and function.

Original languageEnglish (US)
Pages (from-to)2392-2397
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number8
StatePublished - Feb 22 2004


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