Huang P C, Gaitan A E, Hao Y, Petters R M, Wong F
Department of Ophthalmology, Duke University School of Medicine, Durham, NC 27710.
Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8484-8. doi: 10.1073/pnas.90.18.8484.
Photoreceptors of transgenic mice expressing a mutant rhodopsin gene (Pro347-->Ser) slowly degenerate. The mechanism of degeneration was studied by aggregation of embryos of normal and transgenic mice to form chimeras. In these chimeras, mosaicism was observed in the coat color, retinal pigment epithelium, and retina. In the retina, the genotype of adjacent patches of normal and transgenic photoreceptors was determined by in situ hybridization with a transgene-specific RNA probe. Photoreceptors in the chimeric retina degenerated uniformly, independent of the genotype and similar to the photoreceptors in transgenic mice. However, the chimeric retinas showed varying proportions of normal and transgenic cells. The chimeric retina with a nearly even proportion of normal and transgenic photoreceptors displayed uniform but slower degeneration than that observed in a transgenic mouse of the same age. Our results demonstrate non-autonomy of gene action for the mutated rhodopsin gene and imply that cellular interactions between photoreceptors in the retina probably play a role in degeneration.
表达突变视紫红质基因（Pro347→Ser）的转基因小鼠的光感受器会缓慢退化。通过将正常小鼠和转基因小鼠的胚胎聚集形成嵌合体来研究退化机制。在这些嵌合体中，在外套颜色、视网膜色素上皮和视网膜中观察到了嵌合现象。在视网膜中，通过与转基因特异性RNA探针进行原位杂交来确定相邻的正常和转基因光感受器斑块的基因型。嵌合视网膜中的光感受器均匀退化，与基因型无关，且与转基因小鼠中的光感受器相似。然而，嵌合视网膜显示出正常细胞和转基因细胞的不同比例。正常光感受器和转基因光感受器比例几乎相等的嵌合视网膜表现出均匀但比同年龄转基因小鼠中观察到的退化速度更慢。我们的结果证明了突变视紫红质基因的基因作用是非自主性的，并暗示视网膜中光感受器之间的细胞相互作用可能在退化中起作用。
