purpose. The severity of disease in patients with retinitis pigmentosa (RP) can vary significantly, even among patients with the same primary mutations. It is hypothesized that modifier genes play important roles in determining the severity of RP, including the retinitis pigmentosa 1 (RP1) form of disease. To investigate the basis of variation in disease expression for RP1 disease, the authors generated congenic mice with a gene-targeted retinitis pigmentosa 1 homolog (Rp1h) allele (Rp1h tm1Eap) on several different genetic backgrounds and analyzed their retinal phenotypes.

methods. The Rp1h tm1Eap allele was placed onto the C57BL/6J, DBA1/J, and A/J backgrounds. Retinal function of the resultant congenic mice was evaluated using electroretinographic analyses. Retinal structure and ultrastructure were evaluated using light and electron microscopy. Rp1h protein location was determined with immunofluorescence microscopy.

results. Analysis of the retinal phenotype of incipient congenic (N6) B6. 129S-Rp1h+/tm1Eap, DBA. 129S (B6)-Rp1h+/tm1Eap, and A. 129S (B6)-Rp1h+/tm1Eap mice at 1 year of age showed retinal degeneration only in the A. 129S (B6)-Rp1h+/tm1Eap mice. Further analyses revealed that the photoreceptors of the fully congenic A. 129S (B6)-Rp1h+/tm1Eap mice show evidence of degeneration at 6 months of age and are almost completely lost by 18 months of age. In contrast, the photoreceptor cells in the fully congenic B6. 129S-Rp1h+/tm1Eap mice remain healthy up to 18 months.

conclusions. The severity of the retinal degeneration caused by the Rp1h tm1Eap allele is notably dependent on genetic background. The development and characterization of the B6. 129S-Rp1h+/tm1Eap and A. 129S (B6)-Rp1h+/tm1Eap congenic mouse lines will facilitate identification of sequence alterations in genes that modify the severity of RP1 disease.