Generation and phenotypic analysis of CHIF knockout mice.
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.
Aizman
Roman
R
Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel.
Asher
Carol
C
Füzesi
Maria
M
Latter
Hedva
H
Lonai
Peter
P
Karlish
Steven J D
SJ
Garty
Haim
H
D000595:Amino Acid Sequence; D000818:Animals; D001769:Blood; D015139:Blotting, Southern; D004262:DNA Restriction Enzymes / Q000378:metabolism; D004032:Diet; D004039:Diet, Sodium-Restricted; D004622:Embryo, Mammalian / Q000166:cytology; D005091:Exons; D005665:Furosemide / Q000494:pharmacology; D005919:Glomerular Filtration Rate; D007438:Introns; D007679:Kidney Medulla / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D009994:Osmolar Concentration; D010641:Phenotype; D011188:Potassium / Q000008:administration & dosage; D011189:Potassium Chloride / Q000008:administration & dosage; D012333:RNA, Messenger / Q000032:analysis / Q000737:chemistry; D017422:Sequence Analysis, DNA; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism; D014162:Transfection; D014556:Urine
D008565:Membrane Proteins; D012333:RNA, Messenger; C422209:corticosteroid hormone-induced factor; D011189:Potassium Chloride; D005665:Furosemide; D004262:DNA Restriction Enzymes; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium