In:
American Journal of Physiology-Renal Physiology, American Physiological Society, Vol. 298, No. 1 ( 2010-01), p. F24-F34
Abstract:
Claudin-7, a member of the claudin family, is highly expressed in distal nephrons of kidneys and has been reported to be involved in the regulation of paracellular Cl − permeability in cell cultures. To investigate the role of claudin-7 in vivo, we generated claudin-7 knockout mice (Cln7 −/− ) by the gene-targeting deletion method. Here we report that Cln7 −/− mice were born viable, but died within 12 days after birth. Cln7 −/− mice showed severe salt wasting, chronic dehydration, and growth retardation. We found that urine Na + , Cl − , and K + were significantly increased in Cln7 −/− mice compared with that of Cln7 +/+ mice. Blood urea nitrogen and hematocrit were also significantly higher in Cln7 −/− mice. The wrinkled skin was evident when Cln7 −/− mice were ∼1 wk old, indicating that they suffered from chronic fluid loss. Transepidermal water loss measurements showed no difference between Cln7 +/+ and Cln7 −/− skin, suggesting that there was no transepidermal water barrier defect in Cln7 −/− mice. Claudin-7 deletion resulted in the dramatic increase of aldosterone synthase mRNA level as early as 2 days after birth. The significant increases of epithelial Na + channel α, Na + -Cl − cotransporter, and aquaporin 2 mRNA levels revealed a compensatory response to the loss of electrolytes and fluid in Cln7 −/− mice. Na + -K + -ATPase α 1 expression level was also greatly increased in distal convoluted tubules and collecting ducts where claudin-7 is normally expressed. Our study demonstrates that claudin-7 is essential for NaCl homeostasis in distal nephrons, and the paracellular ion transport pathway plays indispensable roles in keeping ionic balance in kidneys.
Type of Medium:
Online Resource
ISSN:
1931-857X
,
1522-1466
DOI:
10.1152/ajprenal.00450.2009
Language:
English
Publisher:
American Physiological Society
Publication Date:
2010
detail.hit.zdb_id:
1477287-5
