APOPTOSIS - FINAL COMMON PATHWAY OF PHOTORECEPTOR DEATH IN RD, RDS, AND RHODOPSIN MUTANT MICE
APOPTOSIS - FINAL COMMON PATHWAY OF PHOTORECEPTOR DEATH IN RD, RDS, AND RHODOPSIN MUTANT MICE
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DOI：
10.1016/0896-6273(93)90072-y
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发表时间：
1993-10-01
期刊：
影响因子：
16.2
通讯作者：
WONG, F
中科院分区：
文献类型：
--
作者：
CHANG, GQ;HAO, Y;WONG, F
视网膜变性、视网膜变性慢(/外周蛋白)和视紫红质基因突变会导致人类和小鼠的光感受器退化。尽管这些突变产生的表型不同，提示了不同的发病机制，但我们提出的证据表明，细胞凋亡可能是疾病过程中将基因型与表型联系起来的最终共同途径。凝胶电泳法观察视网膜DNA核小体间裂解，生物素化聚(DU)标记DNA缺口末端在单细胞水平观察DNA碎裂。在视网膜变性小鼠中，DNA片段化发生在光感受器退行性变期间。在视网膜退化缓慢的小鼠和表达突变的(Pro347Ser)视紫红质基因的转基因小鼠中，在正常的组织发生细胞死亡(也包括细胞凋亡)停止后，DNA发生片段化。由于核小体间裂解导致的DNA片段化是细胞凋亡的一个主要特征，我们的数据表明这三种基因突变都会导致细胞凋亡。
Mutations in the retinal degeneration, retinal degeneration slow(/peripherin) and rhodopsin genes cause photoreceptor degeneration in humans and mice. Although the phenotypes arising from these mutations are different, suggesting different mechanisms of pathogenesis, we present evidence that apoptosis may be the final common pathway of the disease process linking genotype to phenotype. We observed internucleosomal cleavage of retinal DNA by gel electrophoresis and fragmented DNA at the single cell level by labeling the nicked DNA ends with biotinylated poly(dU). In retinal degeneration mice, DNA fragmentation occurred during the period of photoreceptor degeneration. In retinal degeneration slow mice and in transgenic mice expressing a mutant (Pro347Ser) rhodopsin gene, DNA fragmentation occurred after normal histogenetic cell death (also apoptosis) had ceased. Since DNA fragmentation by internucleosomal cleavage is a cardinal feature of apoptosis, our data suggest that all three of these genetic mutations lead to apoptosis.