Establishment of N–ethyl–N–Nitrosourea–Induced Dominantly Inherited Eye Mutations in Mice as Models for Human Eye Diseases

Abstract

Abstract: : Purpose:To develop N–ethyl–N–nitrosourea (ENU)–induced dominantly inherited eye mutations in mice. Methods:A large–scale mouse ENU–mutagenesis program was performed (http://www.gsc.riken.go.jp/Mouse/). Slit–lamp biomicroscopic and/or funduscopic screening were carried out on F1 mice generated by mating ENU–treated adult male C57BL/6 mice with adult female DBA/2J mice. Ocular abnormalities observed in the F1 mice were confirmed to be dominantly inherited by backcrossing the F1 mice to DBA/2J. Mutants were mapped using single nucleotide polymorphism (SNP) markers. Results:Seventeen dominantly inherited mutants having ocular abnormalities such as cataract, microphthalmia, optic disc with temporal white scleral crescent, shiny retinal arteriolar reflexes, and retinal degeneration were identified. The eight mutants with cataracts were mapped to chromosomes 2, 7, 8, and 14. Two mutants with shiny retinal arteriolar reflex were mapped to chromosome 8. Mapping of the other mutants are underway. The Pax6 gene was identified as the gene responsible for three mutants with cataract and/or microphthalmia that were mapped to chromosome 2. Conclusions:A technique to develop ENU–induced dominantly inherited eye mutations in mice has been established. These mice mutants will be valuable for analyzing gene function and can be studied as animal models for hereditary human eye diseases.

Keywords: mutations • cataract • retina