Altered cAMP levels in retinas from transgenic mice expressing a rhodopsin mutant.

Transgenic mice expressing the rhodopsin mutant Pro347Ser (Serine 6) display retinal degeneration through apoptosis that is characteristic of the disease retinitis pigmentosa. By 5 weeks after birth, these mice have lost approximately 35% of their photoreceptor cells. Retinas from these mice showed higher levels of cAMP compared to the levels in retinas of normal mice. Our studies provide evidence that elevated cAMP is common to the apoptotic process that occurs in retinitis pigmentosa. In addition, in vitro studies demonstrate no differences in the ability of the mutant and the wild-type rhodopsin to activate transducin, the rod cell G protein, to be phosphorylated by rhodopsin kinase or to bind arrestin. Mutants of rhodopsin, including Pro347Ser, are mistargeted to the rod inner segment, raising the possibility that rhodopsin triggers apoptosis through activation of signaling pathways not normally under its control.