Genetic factors influence cataract formation in α3 connexin knockout mice

Abstract

Connexin α3 (Cx46 or Gja3) gene targeted null mice developed lens nuclear cataracts shortly after birth. A large variance in the cataracts was observed in α3 null sibs on a mixed 129SvJae × C57BL/6J F3 background. This suggested that the genetic background might influence the cataract phenotype. Therefore, we placed the α3 null mutation into a 129SvJae background, and also backcrossed the mutation for six generations into 129SvJ and C57BL/6J backgrounds. While α3 nulls on the two 129 backgrounds contained severe cataracts associated with γ crystallin cleavage, α3 nulls on the C57B16 background had far milder cataracts with no detectable γ crystallin cleavage. These findings suggest that a genetic modifier exists that influences γ crystallin stability, and that γ crystallin breakdown is associated with severe nuclear cataracts. Dev. Genet. 24:27–32, 1999. © 1999 Wiley-Liss, Inc.