Dense cataract and microphthalmia (dcm) in BALB/c mice is caused by mutations in the GJA8 locus

Abstract

A spontaneous mutation in BALB/c mice that causes congenital dense cataract and microphthalmia (dcm) was reported previously. This abnormality was found to be inheritable and the mode of inheritance indicated that this phenotype is due to mutation of an autosomal recessive gene. We performed genetic screen to identify the underlying mutations through linkage analysis with the dcm progenies of F1 intercross. We identified the region of mutation on chromosome 3 and further mapping and sequence analysis identified the mutation in the GJA8 gene that encodes for connexin 50. The mutation represents a single nucleotide change at position 64 (G to C) that results in a change in the amino acid glycine to arginine at position 22 (G22R) and is identical to the mutation previously characterized as lop10. However, the phenotype of these mice differ from that of lop10 mice and since it is one of the very few genetic models with recessive pattern of inheritance, we propose that dcm mice can serve as a useful model for studying the dynamics and interaction of the gap junction formation in mouse eye development.