Normal light response, photoreceptor integrity, and rhodopsin dephosphorylation in mice lacking both protein phosphatases with EF hands (PPEF-1 and PPEF-2)

Rhodopsin dephosphorylation in Drosophila is a calcium-dependent process th at appears to be catalyzed by the protein product of the rdgC gene. Two ver tebrate rdgC homologs, PPEF-1 and PPEF-2, have been identified. PPEF-1 tran scripts are present at low levels in the retina, while PPEF-2 transcripts a nd PPEF-2 protein are abundant in photoreceptors. To determine if PPEF-2 al one or in combination with PPEF-1 plays a role in rhodopsin dephosphorylati on and to determine if retinal degeneration accompanies mutation of PPEF-1 and/or PPEF-2, we have produced mice carrying targeted disruptions in the P PEF-1 and PPEF-2 genes. Loss of either or both PPEFs has little or no effec t on rod function, as mice lacking both PPEF-1 and PPEF-2 show little or no changes in the electroretinogram and PPEF-2(-/-) mice show normal single-c ell responses to light in suction pipette recordings. Light-dependent rhodo psin phosphorylation and dephosphorylation are also normal or nearly normal as determined by (i) immunostaining of PPEF-2(-/-) retinas with the phosph orho-dopsin-specific antibody RT-97 and (ii) mass spectrometry of C-termina l rhodopsin peptides from mice lacking both PPEF-1 and PPEF-2. Finally, PPE F-2(-/-) retinas show normal histology at I year of age, and retinas from m ice lacking both PPEF-1 and PPEF-2 show normal histology at 3 months of age , the latest time examined. These data indicate that, in contrast to loss o f rdgC function in Drosophila, elimination of PPEF function does not cause retinal degeneration in vertebrates.