Details

Autor(en) / Beteiligte

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

Titel

Loss of NFAT5 Results in Renal Atrophy and Lack of Tonicity-Responsive Gene Expression

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2004-02, Vol.101 (8), p.2392-2397

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2004

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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/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.