A New Mouse Model of Cone Photoreceptor Function Loss (Cpfl2)

Abstract

Abstract: : Purpose: To report the clinical appearance, histology, and gene mapping of a new dominant mouse mutation that causes a progressive cone function loss in mice. Methods: While screening mouse strains and stocks at The Jackson Laboratory for genetic mouse models of human ocular disorders, we have identified a new progressive cone electroretinographic photopic functional loss with retinal spots. This new mutation has been named cone photoreceptor function loss 2 (Cpfl2) since it is the second mutation in mice to affect cone function with dominant inheritance. We characterized the clinical effects of this mutation using serial electroretinography (ERG), fundus photography, histology, and performed genetic analysis including linkage studies. Results: Mice carrying the Cpfl2 mutation show retinal spots around the optic head at 4 months of age. The spots areas extend with age and cover the entire retina by 7 months of age. The cone-mediated photoresponses start to decrease at 2 months of age and are gone by 4 months of age, but rod-mediated photoresponses are normal from 3 weeks to 8 months of age. Histological results show large waves and rosettes in the central retina at 8 months of age. Genetic analysis shows that this disorder is caused by an autosomal dominant mutation that maps to mouse Chromosome 3. Conclusions: The phenotypic characteristics of Cpfl2 mice are similar to those observed in patients with incomplete achromatopsia and progressive cone dystrophy and this mutant may provide a mouse model for these diseases.

Keywords: animal model • retina: distal(photoreceptors, horizontal cell • gene mapping