Claudin-7 knockout by gene targeting

To investigate the claudin-7 function in vivo, we generated a claudin-7 knockout mouse model by gene targeting through homologous recombination. In this study, we report that Cln7-/- pups show Na+, Cl-, and K+ wasting and chronic dehydration phenotypes. The dramatic increase of aldosterone synthase mRNA level suggests that these mice suffer from mishandling of NaCl and fluid in the distal nephrons. Deletion of claudin-7 invokes several compensatory changes, such as increased renin, serum-glucocorticoid-induced kinase 1 (SGK1), epithelial Na+ channel (ENaCα), Na+-Cl- cotransporter (NCC), as well as aquaporin (AQP) 2 mRNA levels, demonstrating the cross talks between paracellular and transcellular ion transport pathways. 8 mouse intestinal samples were analyzed with 4 wildtype (WT) and 4 claudin-7 knockout (KO). Both WT and KO contain 2 small and 2 large intestinal samples.