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Generation and phenotype of a transgenic knockout mouse lacking the mercurial-insensitive water channel aquaporin-4.

Aquaporin-4 (AQP4) is a mercurial-insensitive, water-selective channel that is expressed in astroglia and basolateral plasma membranes of epithelia in the kidney collecting duct, airways, stomach, and colon. A targeting vector for homologous recombination was constructed using a 7-kb SacI AQP4 genomic fragment in which part of the exon 1 coding sequence was deleted. Analysis of 164 live births from AQP4[+/-] matings showed 41 [+/+], 83 [+/-], and 40 [-/-] genotypes. The [-/-] mice expressed small amounts of a truncated AQP4 transcript and lacked detectable AQP4 protein by immunoblot analysis and immunocytochemistry. Water permeability in an AQP4-enriched brain vesicle fraction in [+/+] mice was high and mercurial insensitive, and was decreased by 14-fold in [-/-] mice. AQP4 deletion did not affect growth or tissue morphology at the light microscopic level. Northern blot analysis showed that tissue-specific expression of AQPs 1, 2, 3, and 5 was not affected by AQP4 deletion. Maximum urine osmolality after a 36-h water deprivation was (in mosM, n = 15) [+/+] 3,342+/-209, [+/-] 3, 225+/-167, and [-/-] 2,616+/-229 (P < 0.025), whereas urine osmolalities before water deprivation did not differ among the genotypes. Rotorod analysis of 35- 38-d-old mice revealed no differences in neuromuscular function (performance time in s, n = 8): [+/+] 297+/-25, [+/-] 322+/-28, [-/-] 288+/-37. These results indicate that AQP4 deletion in CD1 mice has little or no effect on development, survival, growth, and neuromuscular function, but produces a small defect in urinary concentrating ability consistent with its expression in the medullary collecting duct.

Pubmed ID: 9276712


  • Ma T
  • Yang B
  • Gillespie A
  • Carlson EJ
  • Epstein CJ
  • Verkman AS


The Journal of clinical investigation

Publication Data

September 1, 1997

Associated Grants

  • Agency: NIDDK NIH HHS, Id: DK-35124
  • Agency: NHLBI NIH HHS, Id: HL-42368
  • Agency: NHLBI NIH HHS, Id: HL-51854

Mesh Terms

  • Animals
  • Aquaporin 2
  • Aquaporin 4
  • Aquaporin 6
  • Aquaporins
  • Female
  • Ion Channels
  • Kidney Concentrating Ability
  • Male
  • Mercury
  • Mice
  • Mice, Knockout
  • Phenotype
  • RNA, Messenger
  • Water-Electrolyte Balance