title: Genetic and phenotypic analysis of Tcm, a mutation affecting early eye development.
abstract: Tcm (total cataract with microphthalmia) is an autosomal dominant mouse eye mutation. Heterozygous Tcm/+ mice are born with several eye malformations including microphthalmia, retinal and iris dysplasia, total lens cataract, and ventral coloboma. The Tcm mutation was previously mapped to a 26-Mb region on Chr 4 between D4Mit235 and D4Mit106. In this study, we characterize the Tcm/ Tcm homozygous mutant and find they are viable but severely microphthalmic. The developing eye in the Tcm/Tcm homozygote shows defects during early eye development, before formation of the optic cup. Further genetic mapping reduced the Tcm critical region to a 1.3-Mb region bordered by SNPs rs3666764 and rs3713818. This critical region contains two known genes (Asph and Gfd6) and three predicted genes, all of which are positional candidates for Tcm. Sequence analysis of Tcm genomic DNA revealed no mutations in the coding regions and splice site junctions of the five candidate genes. These results indicate that the causitive Tcm mutation falls within a noncoding regulatory region of one of the five candidate genes or in an undescribed gene.
authors.affiliation: F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania School of Medicine, Stellar-Chance Bldg. Rm. 315, 422 Curie Blvd., Philadelphia, Pennsylvania 19104, USA.
authors.forename: Ken S
authors.initials: KS
authors.lastname: Wang
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Zahn
authors.forename: Jack
authors.initials: J
authors.lastname: Favor
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Huang
authors.forename: Dwight
authors.initials: D
authors.lastname: Stambolian
mesh_terms: D000375:Aging; D000818:Animals; D001483:Base Sequence; D002386:Cataract / Q000235:genetics*; D002874:Chromosome Mapping; D017931:DNA Primers; D047108:Embryonic Development / Q000235:genetics; D005123:Eye / Q000196:embryology* / Q000254:growth & development*; D005819:Genetic Markers; D051379:Mice; D008809:Mice, Inbred C3H / Q000235:genetics*; D008850:Microphthalmos / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D005819:Genetic Markers