| First Author | López-Rodríguez C | Year | 2004 |
| Journal | Proc Natl Acad Sci U S A | Volume | 101 |
| Issue | 8 | Pages | 2392-7 |
| PubMed ID | 14983020 | Mgi Jnum | J:88636 |
| Mgi Id | MGI:3036411 | Doi | 10.1073/pnas.0308703100 |
| Citation | Lopez-Rodriguez C, et al. (2004) Loss of NFAT5 results in renal atrophy and lack of tonicity-responsive gene expression. Proc Natl Acad Sci U S A 101(8):2392-7 |
| abstractText | 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. |
