Hobson A H, Donovan M, Humphries M M, Tuohy G, McNally N, Carmody R, Cotter T, Farrar G J, Kenna P F, Humphries P
The Ocular Genetics Unit, Trinity College, Dublin, 2, Ireland.
Exp Eye Res. 2000 Sep;71(3):247-54. doi: 10.1006/exer.2000.0878.
A combined total of approximately 100 mutations have been encountered within the rhodopsin gene in retinitis pigmentosa (RP) and congenital night blindness. Mice carrying a targeted disruption of the rhodopsin gene phenotypically mimic RP, losing their photoreceptors over a period of 3 months and having no recordable rod electroretinogram. These animals will serve as a model for both recessive and dominant disease (in the latter case, the presence of normal and mutant human rod opsin transgenes on the murine Rho(-/-)background). Precise knowledge of apoptotic photoreceptor cell death, together with factors which may influence apoptosis will be required for optimum utility of Rho(-/-)mice as a model for therapeutic genetic intervention. A peak phase of apoptosis of the photoreceptors of Rho(-/-)mice was shown to occur at 24 days post-birth. The extent of apoptosis appeared to be similar, irrespective of whether or not the rod opsin knockout was present on a c-fos(+/+)or c-fos(-/-)genetic background, the latter known to favor survival of photoreceptors following exposure of mouse retinas to excessive light. These data clearly support the existence in animals of distinct apoptotic pathways in light-induced, as opposed to mutation-induced apoptosis, and together with similar observations recently reported in studies of the naturally occurring rd mouse, may assist in focusing future research on precisely defining the distinct molecular pathways giving rise to such dichotomy.
在视网膜色素变性（RP）和先天性夜盲症中，视紫红质基因总共出现了约100种突变。携带视紫红质基因靶向破坏的小鼠在表型上模拟RP，在3个月的时间内失去其光感受器，并且没有可记录的视杆细胞视网膜电图。这些动物将作为隐性和显性疾病的模型（在后一种情况下，在小鼠Rho（-/-）背景上存在正常和突变的人类视杆视蛋白转基因）。为了将Rho（-/-）小鼠作为治疗性基因干预的模型发挥最佳效用，需要精确了解凋亡性光感受器细胞死亡以及可能影响细胞凋亡的因素。研究表明，Rho（-/-）小鼠光感受器的凋亡高峰期出现在出生后24天。无论视杆视蛋白敲除是存在于c-fos（+/+）还是c-fos（-/-）基因背景上，凋亡程度似乎都是相似的，后者已知有利于小鼠视网膜暴露于强光后光感受器的存活。这些数据清楚地支持了在动物中存在与突变诱导的凋亡相反的光诱导凋亡的不同途径，并且与最近在对自然发生的rd小鼠的研究中报道的类似观察结果一起，可能有助于将未来的研究重点放在精确界定导致这种二分法的不同分子途径上。
