Comparative structural and functional analysis of photoreceptor neurons ofRho-/- mice reveal increased survival on C57BL/6J in comparison to 129Sv genetic background

To explore the possible influence of defined genetic backgrounds on photore ceptor viability and function in mice carrying a targeted disruption of the rhodopsin gene, the severities of retinopathies in Rho-/- mice on C57BL/6J and 129Sv congenic backgrounds were compared by light microscopy and elect roretinography and qualitatively by in situ end labeling of DNA in apoptoti c photoreceptor nuclei of retinal sections. Cone photoreceptor viability an d function were shown to deteriorate more slowly on the C57BL/6J background in comparison to that of the 129Sv, with significantly greater numbers of outer nuclear layer nuclei in the retinas of C57BL/6J mice at 3 and 4 month s of age. Both amplitude and waveform features of the ERG were shown to be remarkably different in the two strains, indicating an approximately 6-fold difference in C57BL/6J Rho-/- mice compared to 129Sv Rho-/- mice at 80 day s. Thus, in comparison with the 129Sv strain, genetic modifiers appear to c onstitute a component of the C57BL/6J background, the expression of which s ignificantly, protects cone photoreceptors from apoptotic death in a mutati on-induced murine retinopathy. The differences in phenotype revealed in thi s study are sufficient in principle to provide a basis for comparisons to b e made between QTLs in light-induced and mutation-induced systems.