Compound heterozygotes show age-dependent phenotypes.

A–D. Cross-sections of 8-week-old retinas stained with H&E show disrupted morphology similar to that seen at 4 weeks in Cbp CH and R-DCKO mice. Scale bar = 50 μm. E–G. ERG testing shows persistence of the functional impairment in R-DCKO retinas (panels F and G). Dark-adapted b-wave deficits in some p300 CH mice tested at this time are reflected in the slightly decreased average and broad error bars for this genotype (Panel F orange line). Two-way repeated measures ANOVA indicated significance at p<0.0001 for dark-adapted a-waves (Panel E), b-waves (Panel F), and light-adapted b-waves (Panel G). H–K. Cross-sections of 12-week-old retinas stained with H&E. Morphologic abnormalities in Cbp CH retinas (panel J) have resolved, although whorls and rosettes are still seen in R-DCKO retinas (panel K). Scale bar = 50 μm. L–N. ERG testing at 12 weeks revealed decreases in function in both Cbp CH and P300 CH, and R-DCKO retinas have lost cone responses in addition to rod function. Two-way repeated measures ANOVA indicated significance at p<0.0001 for dark-adapted a-waves (Panel L), b-waves (Panel M), and light-adapted b-waves (Panel N). Asterisks (*) indicate p<0.001 vs. Cre negative controls in post-hoc tests.