ALTERED CAMP LEVELS IN RETINAS FROM TRANSGENIC MICE EXPRESSING A RHODOPSIN MUTANT

Transgenic mice expressing the rhodopsin mutant Pro347Ser (Serine 6) d isplay retinal degeneration through apoptosis that is characteristic o f the disease retinitis pigmentosa. By 5 weeks after birth, these mice have lost approximately 35% of their photoreceptor cells. Retinas fro m these mice showed higher levels of cAMP compared to the levels in re tinas 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 abil ity 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 mistarg eted to the rod inner segment, raising the possibility that rhodopsin triggers apoptosis through activation of signaling pathways not normal ly under its control. (C) 1995 Academic Press, Inc.