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Am J Physiol Renal Physiol 283: F569-F577, 2002. First published March 19, 2002; doi:10.1152/ajprenal.00376.2001
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Vol. 283, Issue 3, F569-F577, September 2002

Generation and phenotypic analysis of CHIF knockout mice

Roman Aizman1,2,*, Carol Asher1,*, Maria Füzesi1, Hedva Latter1, Peter Lonai3, Steven J. D. Karlish1, and Haim Garty1

Departments of 1 Biological Chemistry and 3 Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel; and 2 Department of Anatomy, Physiology and Health Education, Novosibirsk State Pedagogical University, Russian Federation

Corticosteroid hormone-induced factor (CHIF) is a short epithelial-specific protein that is independently induced by aldosterone and a high-K+ diet. It is a member of the FXYD family of single-span transmembrane proteins that include phospholemman, Mat-8, and the gamma -subunit of Na+-K+-ATPase. A number of studies have suggested that these proteins are involved in the regulation of ion transport and, in particular, functionally interact with the Na+-K+-ATPase. The present study describes the characterization, targeted disruption, and phenotypic analysis of the mouse CHIF gene. The CHIF knockout mice are viable and not distinguishable from wild-type littermates under normal conditions. Under K+ loading, they have a twofold higher urine volume and an increased glomerular filtration rate. Similar but smaller effects are observed in mice fed a low-Na+ diet. Treating K+-loaded mice for 10 days with furosemide resulted in lethality in the knockout mice (17 of 39) but not in the wild-type group (1 of 39). The data are consistent with an effect of CHIF on the Na+-K+-ATPase that is specific to the outer and inner medullary duct, its major expression site.

FXYD proteins; sodium-potassium-adenosine-5'-triphosphatase; gamma -subunit; furosemide; corticosteroid hormone-induced factor; aldosterone

* R. Aizman and C. Asher contributed equally to this work.




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