Severely impaired urine-concentrating ability in mice lacking the CLC-K1 chloride channel.
To analyze the physiological functions of CLC-K1 in vivo, we generated mice lacking CLC-K1 by targeted gene disruption. Homozygous mutant Clcnk1-/- mice produced approximately 5 times more urine than Clcnk1+/- and Clcnk1+/+ mice. After 24-hour water deprivation, Clcnk1-/- mice became severely dehydrated and lethargic. Intraperitoneal injection of the V2 agonist, deamino-Cys(1), D-Arg(8) vasopressin, induced an increase in urine osmolarity in Clcnk1+/- and Clcnk1+/+ mice from approximately 1,000 to approximately 3,000 mosm/kg H(2)O, whereas the increase in Clcnk1-/- mice was only from approximately 600 to approximately 840 mosm/kg H(2)O, indicating nephrogenic diabetes insipidus in Clcnk1-/- mice. These results clearly established that CLC-K1 plays a major role in the urinary-concentrating mechanisms.
Uchida
S
S
Second Department of Internal Medicine, Tokyo Medical and Dental University, School of Medicine, Tokyo, Japan. suchida.med2@med.tmd.ac.jp
Marumo
F
F
D000818:Animals; D018118:Chloride Channels / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D002712:Chlorides / Q000378:metabolism; D003681:Dehydration / Q000097:blood / Q000652:urine; D017353:Gene Deletion; D006801:Humans; D007668:Kidney / Q000502:physiology; D007671:Kidney Concentrating Ability / Q000502:physiology*; D008138:Loop of Henle / Q000378:metabolism; D009154:Mutation / Q000502:physiology
C489932:CLCNKA protein, human; D018118:Chloride Channels; D002712:Chlorides