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

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.

SUBMITTER: Lopez-Rodriguez C

PROVIDER: S-EPMC356961 | biostudies-literature | 2004 Feb

REPOSITORIES: biostudies-literature

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

López-Rodríguez Cristina C Antos Christopher L CL Shelton John M JM Richardson James A JA Lin Fangming F Novobrantseva Tatiana I TI Bronson Roderick T RT Igarashi Peter P Rao Anjana A Olson Eric N EN

Proceedings of the National Academy of Sciences of the United States of America 20040201 8

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 ...[more]

PMID: 14983020

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

Publications

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

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