Weiss E R, Hao Y, Dickerson C D, Osawa S, Shi W, Zhang L, Wong F
Department of Cell Biology and Anatomy, University of North Carolina at Chapel Hill 27599-7090, USA.
Biochem Biophys Res Commun. 1995 Nov 22;216(3):755-61. doi: 10.1006/bbrc.1995.2686.
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.
表达视紫红质突变体Pro347Ser（丝氨酸6）的转基因小鼠通过凋亡表现出视网膜变性，这是色素性视网膜炎疾病的特征。出生后5周，这些小鼠已经失去了大约35%的光感受器细胞。与正常小鼠视网膜中的水平相比，这些小鼠的视网膜显示出更高水平的环磷酸腺苷（cAMP）。我们的研究提供了证据，表明cAMP升高在色素性视网膜炎中发生的凋亡过程中是常见的。此外，体外研究表明，突变型和野生型视紫红质激活转导蛋白（视杆细胞G蛋白）、被视紫红质激酶磷酸化或结合抑制蛋白的能力没有差异。视紫红质突变体，包括Pro347Ser，被错误靶向到视杆细胞内节，这增加了视紫红质通过激活通常不在其控制下的信号通路触发凋亡的可能性。
