Two interactive genes responsible for a new inherited cataract (RCT) in the mouse.

Abstract

We discovered a mutant mouse, RCT (Rinshoken cataract), with a new congenital cataract in strain SJL/J. The opacity of the lens associated with microphthalmia could be observed visually at 3 to 3.5 months of age. Marked degeneration of the lens, including loss of the fine structure of the lens fibers and swelling of epithelial cells with vacuoles of various sizes in the cortex, but no other defects except photoreceptor degeneration in the retina, was detected. Histological change in the lens was first observed at 2 days after birth. No sex-related differences were detected, and normal phenotypes in the F1 progeny of RCT and normal mice indicated that the cataract was recessive. The chromosomal location of the causative gene was determined by interval mapping by using intersubspecific backcross progeny of RCT and MSM/Ms, an inbred strain from the Japanese wild mouse Mus musculus molossinus. Backcross progeny were divided into three groups according to phenotype: mice (1) with an early-onset cataract, which can be detected visually as in RCT mice, (2) with a late-onset cataract, which can be detected histologically but not visually, and (3) with a normal lens. Three phenotypes were found to be expressed by allele combinations of two recessive genes, rct and mrct (a modifier of rct). The rct locus essential for the onset of the cataract was tightly linked to D4Mit278 on Chromosome (Chr) 4 with no recombination. The mrct locus was closely linked to D5Mit239 (chi2 = 66.3, P << 0.00001) on Chr 5.