title: Cat3vl and Cat3vao cataract mutations on mouse chromosome 10: phenotypic characterization, linkage studies and analysis of candidate genes.
abstract: Cat3vl and Cat3vao are two allelic, dominant cataract mutations that arose independently in the F1 generation after gamma-irradiation of male mice. The cataracts are already present at birth. Examination of the eyes with a slit lamp revealed completely vacuolated lenses in Cat3vl mutants and anteriorly located opacity in Cat3vao mutants. The 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 Cat3vl homozygotes. Cat3vao was assigned to the distal part of mouse chromosome 10, 3.2 +/- 0.9 cM away from the visible marker Steel (SlgbH). Using polymorphic markers the following locus order was found: D10Mit230-(0.2 +/- 0.1 cM)-Cat3vao-(2.5 +/- 0.6 cM)-D10Mit70. No recombinants were found between Cat3vao and the markers D10Mit4l and D10Mit95 among 921 offspring. The results exclude allelism of Cat3vao with CatLop or To2, which also map to chromosome 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 proteoglycans lumican and decorin, the nuclear orphan receptor Tr2-11 and the transcription factor Elk3. Based on syntenic homology of the Cat3 region to the human chromosome 12q, the Cat3 mutants are discussed as mouse models for cornea plana congenita in man. The recovery of the Cat3 mutations demonstrates the importance of the corresponding locus for proper eye development.
authors.affiliation: GSF-National Research Center for Environment and Health, Institute of Mammalian Genetics, Neuherberg, Germany. jana.loester@gsf.de
authors.forename: J
authors.initials: J
authors.lastname: Löster
authors.forename: T
authors.initials: T
authors.lastname: Immervoll
authors.forename: T
authors.initials: T
authors.lastname: Schmitt-John
authors.forename: J
authors.initials: J
authors.lastname: Graw
mesh_terms: D000818:Animals; D002386:Cataract / Q000235:genetics*; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics; D002875:Chromosomes; D058575:Decorin; D016326:Extracellular Matrix Proteins; D005799:Genes, Dominant; D008040:Genetic Linkage; D005819:Genetic Markers; D007632:Keratan Sulfate / Q000235:genetics; D000071234:Lumican; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D009154:Mutation; D010641:Phenotype; D011509:Proteoglycans / Q000235:genetics
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; C546878:DCN protein, human; C546879:Dcn protein, mouse; D058575:Decorin; D016326:Extracellular Matrix Proteins; D005819:Genetic Markers; C000604306:LUM protein, human; C000604307:Lum protein, mouse; D000071234:Lumican; D011509:Proteoglycans; D007632:Keratan Sulfate