Genetic factors influence cataract formation in alpha(3) connexin knockoutmice

Connexin alpha(3) (Cx46 or Gja3) gene targeted null mice developed lens nuc lear cataracts shortly after birth. A large variance in the cataracts was o bserved in alpha(3) null sibs on a mixed 129Svjae x C57BL/6J F3 background. This suggested that the genetic background might influence the cataract ph enotype. Therefore, we placed the alpha(3) null mutation into a 129SvJae ba ckground, and also backcrossed the mutation for six generations into 120SvJ 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 detecta ble gamma crystallin cleavage. These findings suggest thai a genetic modifi er exists that influences gamma crystallin stability, and that gamma crysta llin breakdown is associated with severe nuclear cataracts. (C) 1999 Wiley- Liss, Inc.