CAT3(VL) AND CAT3(VAO) CATARACT MUTATIONS ON MOUSE-CHROMOSOME-10 - PHENOTYPIC CHARACTERIZATION, LINKAGE STUDIES AND ANALYSIS OF CANDIDATE GENES

Cat3(vl) and Cat3(vao) are two allelic, dominant cataract mutations th at arose independently in the F-1 generation after gamma-irradiation o f male mice. The cataracts are already present at birth. Examination o f the eyes with a slit lamp revealed completely vacuolated lenses in C at3(vl) mutants and anteriorly located opacity in Cat3(vao) mutants. T he appearance of the opacities does not differ between the individuals or between heterozygotes and homozygotes. Penetrance of the mutations is complete. Viability and fertility of the mutants are normal except in the case of the Cat3(vl) homozygotes. Cat3(vao) was assigned to th e distal part of mouse chromosome 10, 3.2 +/- 0.9 cM away from the vis ible marker Steel (Sl(gbH)). Using polymorphic markers the following l ocus order was found: D10Mit230-(0.2 +/- 0.1 cM)-Cat3(vao)-(2.5 +/- 0. 6 cM)-D10Mit70. No recombinants were found between Cat3(vao) and the m arkers D10Mit41 and D10Mit95 among 921 offspring. The results exclude allelism of Cat3(vao) with Cat(Lop) or To2, which also map to chromoso me 10. Candidate genes were tested by examination of their expression in the eye of newborn mice and by analysis of cDNA sequences. So far, negative results have been obtained for the genes encoding the proteog lycans lumican and decorin, the nuclear orphan receptor Tr2-11 and the transcription factor Elk3. Based on syntenic homology of the Cat3 reg ion to the human chromosome 12q, the Cat3 mutants are discussed as mou se models for col nea plana congenita in man. The recovery of the Cat3 mutations demonstrates the importance of the corresponding locus for proper eye development.