TY - JOUR
T1 - Loss of NFAT5 results in renal atrophy and lack of tonicity-responsive gene expression
AU - López-Rodríguez, Cristina
AU - Antos, Christopher L.
AU - Shelton, John M.
AU - Richardson, James A.
AU - Lin, Fangming
AU - Novobrantseva, Tatiana I.
AU - Bronson, Roderick T.
AU - Igarashi, Peter
AU - Rao, Anjana
AU - Olson, Eric N.
PY - 2004/2/22
Y1 - 2004/2/22
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/4644333445
UR - https://www.scopus.com/pages/publications/4644333445#tab=citedBy
U2 - 10.1073/pnas.0308703100
DO - 10.1073/pnas.0308703100
M3 - Article
C2 - 14983020
AN - SCOPUS:4644333445
SN - 0027-8424
VL - 101
SP - 2392
EP - 2397
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 8
ER -