A New Mouse Model of Cone Photoreceptor Fuction Loss (cpfl7)

Abstract

Purpose:: To characterize the genetics and phenotype of a new mouse mutant with a progressive cone function loss, cpfl7, that is associated with a neurological phenotype seen as an abnormal gait.

Methods:: We have identified a new mouse model of a progressive cone electroretinographic photopic functional loss by screening mouse strains and stocks at The Jackson Laboratory for genetic mouse models of human ocular disorders. We characterized the clinical effects of this mutation using serial electroretinography (ERG), fundus photography, and histology, and performed genetic analysis including linkage studies.

Results:: This new mutation has been named cone photoreceptor function loss 7 (cpfl7) because it is the seventh mutation in mice to affect cone function; it shows autosomal recessive inheritance. Mice homozygous for the cpfl7 mutation show an abnormal light-adapted ERG response and a normal a-wave but lower b-wave dark-adapted ERG response starting at 3 weeks of age. Histological results show Ganglion cell disruption and retinal segment degeneration in the peripheral retina at 3 months of age. The neurological phenotypes include leg clasping when picked up by the tail and high stepping when it walks on shavings. Genetic analysis shows that this disorder is caused by an autosomal recessive mutation that maps to mouse Chromosome 19.

Conclusions:: Cone photoreceptor function loss 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 cone photoreceptor function loss associated with neurological defects.

Keywords: gene mapping • photoreceptors: visual performance • retina