Genetic factors influence cataract formation in alpha 3 connexin knockout mice

Dev Genet. 1999;24(1-2):27-32. doi: 10.1002/(SICI)1520-6408(1999)24:1/2<27::AID-DVG4>3.0.CO;2-7.

Abstract

Connexin alpha 3 (Cx46 or Gja3) gene targeted null mice developed lens nuclear cataracts shortly after birth. A large variance in the cataracts was observed in alpha 3 null sibs on a mixed 129SvJae X C57BL/6J F3 background. This suggested that the genetic background might influence the cataract phenotype. Therefore, we placed the alpha 3 null mutation into a 129SvJae background, and also backcrossed the mutation for six generations into 129SvJ and C57BL/6J backgrounds. While alpha 3 nulls on the two 129 backgrounds contained severe cataracts associated with gamma crystallin cleavage, alpha 3 nulls on the C57B16 background had far milder cataracts with no detectable gamma crystallin cleavage. These findings suggest that a genetic modifier exists that influences gamma crystallin stability, and that gamma crystallin breakdown is associated with severe nuclear cataracts.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blotting, Western
  • Cataract / genetics*
  • Cataract / metabolism
  • Connexins / genetics*
  • Connexins / physiology
  • Crosses, Genetic
  • Crystallins / analysis
  • Crystallins / metabolism*
  • Female
  • Lens, Crystalline / chemistry*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Mice, Knockout
  • Phenotype

Substances

  • Connexins
  • Crystallins
  • GJA3 protein, human