Dominant Mutation Induced by Chemical Mutagenesis Affecting Mouse ERG and Fundus

Abstract

Abstract: : Purpose: We use mutagenesis and screeening to create mouse models of human diseases and allow genetic dissection of the visual system. Methods: C57BL/6J mice were mutagenized with a chemical mutagen, ENU, and bred for 3 generations to generate animals homozygous for recessive mutations. At ca. 12 weeks of age the dark- adapted electroretinogram of each G3 mouse was measured and quantified and the fundus was photographed and anaylzed for abnormalities. The offspring of affected mice were bred to test for transmission of abnormal traits. Results: In one pedigree 5 male and 2 female siblings with no detectable ERG were isolated. Their fundi showed narrowed retinal vessels and a pattern of pigmentation consistent with photoreceptor degeneration. These traits were inherited by their G4 offspring in manner consistent with a dominant mode of inheritance. In addition to this mutant several other putative mutants were isolated with other ERG abnormalities and/or abnormalities of the fundus. These putative mutants are now being tested for genetic transmission. Conclusion: A mouse mutant model of autosomal dominant retinal degenerative disorders has been generated and several other mutants have probably already been generated. The genetic tools available for the mouse make it possible to identify the affected genes and determine the roles of their gene products.

Keywords: genetics • electroretinography: non-clinical • photoreceptors