A New Mouse Model of Retinal Degeneration (RD14) Associated With Neurological Defects

Abstract

Abstract: : Purpose: To characterize the genetics and phenotype of a new mouse mutant with a retinal degeneration associated with extensive, scattered, small white retinal spots, seen ophthalmoscopically, combined with a neurological disorder. Methods: While screening mouse strains and stocks at The Jackson Laboratory for genetic mouse models of human ocular disorders, we have identified a unique mouse retinal degeneration (allele symbol: rd14). The phenotype was documented using electroretinography, histology, and fundus photography, while the genetic characterization and linkage analysis were performed using linkage studies and gene identification. Results: The inheritance pattern of rd14 mutant allele is autosomal recessive. Linkage studies mapped this new mutation to mouse Chromosome 18, in a region between markers D18Mit103 and D18Mit186, suggesting the human homolog may be on chromosome 18q21. The two candidate genes are methyl–CpG–binding domain 2 (Mbd2) and 4930503L19Rik. Ophthalmoscopic examination of mice homozygous for rd14 mutation revealed white retinal spots. Histologic examination revealed large cells in the subretinal space, juxtaposed to the retinal pigment epithelium. White dots seen on fundus examination corresponded both in distribution and size to these large cells. Blood was observed on some retinas, which decreased cone and rod function otherwise rd14 has a normal ERG. Homozygous mutants also display a hopping gait when young, but appear neurologically normal after 2–3 weeks of age. Conclusions: Retinal degeneration and the neurological phenotype combined with our genetic data suggest that this is a new mutation not previously described in mouse or human. This provides a novel mouse model for a retinal degeneration associated with neurological defects.

Keywords: retinal degenerations: hereditary • gene mapping • genetics