Loss of NFAT5 results in renal atrophy and lack of tonicity-responsive gene expression.
Document Type
Article
Publication Date
2004
First Page
2392
Last Page
2397
JAX Source
Proc Natl Acad Sci U S A 2004 Feb; 101(8):2392-7
Abstract
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 aldose reductase, Na+/Cl--coupled betaine/gamma-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.
Recommended Citation
Lopez RC,
Antos CL,
Shelton JM,
Richardson JA,
Lin F,
Novobrantseva TI,
Bronson RT,
Igarashi P,
Rao A,
Olson EN.
Loss of NFAT5 results in renal atrophy and lack of tonicity-responsive gene expression. Proc Natl Acad Sci U S A 2004 Feb; 101(8):2392-7