Bilateral congenital cataracts result from a gain-of-function mutation in the gene for aquaporin-0 in mice

Tadashi Okamura, Ichiro Miyoshi, Kazuhiro Takahashi, Yasumasa Mototani, Sadao Ishigaki, Yasuhiro Kon, Noriyuki Kasai

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Cataract Tohoku (CatTohm) is a dominant cataract mutation that leads to severe degeneration of lens fiber cells. Linkage analysis showed that the CatTohm mutation is located on mouse chromosome 10, close to the gene for aquaporin-0 (Aqp0), which encodes a membrane protein that is expressed specifically in lens fiber cells. Sequence analysis of Aqp0 revealed a 12-bp deletion without any change in the reading frame, which resulted in a deletion of four amino acids within the second transmembrane region of the AQP0 protein. Targeted expression of the mutated Aqp0 caused lens opacity in transgenic mice, the pathological severity of which depended on the expression level of the transgene. The mutated AQP0 protein was localized to the intracellular and perinuclear spaces rather than to the plasma membranes of the lens fiber cells. The cataract phenotype of CatTohm is caused by a gain-of-function mutation in the mutated AQP0 protein and not by a loss-of-function mutation.

Original languageEnglish
Pages (from-to)361-368
Number of pages8
JournalGenomics
Volume81
Issue number4
DOIs
Publication statusPublished - 2003 Apr 1

Keywords

  • Aquaporin-0
  • Cataracts
  • Gain-of function mutation
  • Major intrinsic protein
  • Transgenic mice

ASJC Scopus subject areas

  • Genetics

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