Purpose: In humans, mutations in protocadherin 15 are known to result in Usher Syndrome type 1F (USH1F). Patients with USH1F are born with profound hearing loss and have visual problems that develop in late childhood. Based on the phenotypic hearing loss and an associated mutation in protocadherin 15 (Pcdh15), the Ames waltzer mice have been presented as potential models for USH1F. To determine whether the Ames waltzer is a model for retinopathy in USH1F, retinal structure and function were assessed in all four available alleles of the mouse.
Methods: Activity of both the rod and cone pathways was evaluated by measuring electroretinograms (ERGs) in response to strobe flashes under dark- and light-adapted conditions, respectively. Retinas were processed with standard histochemical procedures, and retinal morphology was examined. The neural retina was dissected from normal pigmented mice at postnatal day (P)0, P5, P7, P20, P40, and P70, and the presence of Pcdh15 was determined by RT-PCR.
Results: The amplitude and implicit time of both the rod- and cone-mediated ERG a- and b-waves were comparable between Ames waltzer mutants and heterozygous littermates as old as 13 months. No evidence of retinal degeneration or disorganization was detected in mutant mice. Measures of retinal layer thicknesses were similar in mutant and wild-type control animals. Retinal expression of Pcdh15 was observed at all ages examined between P0 and P70.
Conclusions: Although Pcdh15 is present in neural retina, its role remains unclear. Mutations in the Pcdh15 did not result in retinal abnormalities in the four alleles of Ames waltzer tested in this study. The explanation for the absence of retinal phenotype in the Ames mouse should be helpful in understanding USH1F and developing treatments for this disorder.