Generation and phenotypic analysis of CHIF knockout mice

Am J Physiol Renal Physiol. 2002 Sep;283(3):F569-77. doi: 10.1152/ajprenal.00376.2001.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Blood
  • Blotting, Southern
  • DNA Restriction Enzymes / metabolism
  • Diet
  • Diet, Sodium-Restricted
  • Embryo, Mammalian / cytology
  • Exons
  • Furosemide / pharmacology
  • Glomerular Filtration Rate
  • Introns
  • Kidney Medulla / metabolism
  • Membrane Proteins / chemistry
  • Membrane Proteins / deficiency
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • Nucleic Acid Hybridization
  • Osmolar Concentration
  • Phenotype*
  • Potassium / administration & dosage
  • Potassium Chloride / administration & dosage
  • RNA, Messenger / analysis
  • RNA, Messenger / chemistry
  • Sequence Analysis, DNA
  • Sodium-Potassium-Exchanging ATPase / metabolism
  • Stem Cells / metabolism
  • Transfection
  • Urine

Substances

  • Membrane Proteins
  • RNA, Messenger
  • corticosteroid hormone-induced factor
  • Potassium Chloride
  • Furosemide
  • DNA Restriction Enzymes
  • Sodium-Potassium-Exchanging ATPase
  • Potassium