Knockout of both Ep300 and Cbp in rods disrupts photoreceptor architecture and function.

A–G. Cross-sections of 4-week-old retinas of the indicated genotypes (see Table 1), stained with hematoxylin and eosin (H&E). H. Section from the same R-DCKO eye as in panel G, fluorescently labeled with anti-PKCα (green, for bipolar cells) and DAPI (red), to show the boundary between the outer and inner nuclear layers. Scale bar = 50 μm for all 8 panels. I–K. Immunofluorescent staining for p300 protein verified expression in all nuclei in Cre neg controls (I). Ep300 expression is lost in the outer nuclear layer (ONL) of p300KO (J) and R-DCKO (K) retinas. L. R-DCKO section stained for p300 (green) and cone arrestin (CARR, red), showing that the few remaining p300-positive cells in the outer retina are cones. Scale bar = 20 μm for all 4 panels. OS, outer segments; ONL, outer nuclear layer; OPL, outer plexiform layer; INL, inner nuclear layer; IPL, inner plexiform layer; GC, ganglion cell layer. M–O. Amplitudes of dark-adapted (“Dark”) and light-adapted (“Light”) flash electroretinograms (ERG) at 4 weeks of age. Flash intensities (log [CdSec/M2]) are indicated on the X-axis. Error bars indicate +/− 1SD of the mean amplitude for 6 animals of each genotype tested. Two-way repeated measures ANOVA showed significant interactions between genotype and log light level at pCre negative controls in post-hoc tests.