ABNORMAL EYE DEVELOPMENT ASSOCIATED WITH CAT4(A), A DOMINANT MOUSE CATARACT MUTATION ON CHROMOSOME-8

PURPOSE. Cat4(a), one of four mutant alleles at the mouse Cat4 locus, causes central corneal opacity and anterior polar cataract in heterozy gotes and microphthalmia in homozygotes. The Cat4 locus has been mappe d to chromosome 8, 31 cM from the centromere. In this study ocular dev elopment of Cat4(a) mutant mice was investigated to characterize the d efects in eye morphogenesis. METHODS. Serial sections from eyes of wil d-type, heterozygous, and homozygous littermates were examined by mean s of light microscopy at selected intervals from embryonic day 11 to p ostnatal day 1. Eyes of adult heterozygous and homozygous mice also we re evaluated histologically. RESULTS. Failure of separation of the len s vesicle from the surface ectoderm was the earliest structural defect observed. In heterozygous embryos, the abnormality was limited to per sistent connection of the anterior pole of the lens to the cornea. Adu lt heterozygotes had defects in the central corneal stroma and endothe lium and anterior polar cataracts with or without keratolenticular adh esion. In homozygous embryos, the persistent connection of lens to sur face ectoderm was associated with aborted lens development, failure of closure of the optic fissure, and impairment of growth of the eyecup. Microphthalmic eyes of adult homozygous mice had a poorly developed c ornea, and the anterior chamber and vitreous compartment were absent. An extensively folded retina and remnants of a degenerated lens filled the interior of the globe. CONCLUSIONS. A developmental defect inhibi ts separation of the lens vesicle from surface ectoderm in mice hetero zygous or homozygous for the Cat4(a) mutation. In homozygotes subseque nt lens and eye morphogenesis are also severely affected. Cat4(a) show s phenotypical similarity to several other independent mouse mutations including Small eye, a mutation of the Pax6 gene. Cat4 may be one of several genes involved in a common developmental path and may be part of the Pax6-regulated gene cascade governing eye morphogenesis.