Cell type-specific effects of Rb deletion in the murine retina
Cell type-specific effects of Rb deletion in the murine retina
复制标题
DOI：
10.1101/gad.1203304
复制
发表时间：
2004-07-15
影响因子：
10.5
通讯作者：
Jacks, T
中科院分区：
文献类型：
--
作者：
MacPherson, D;Sage, J;Jacks, T
人类视网膜的某些细胞对视网膜母细胞瘤肿瘤抑制基因RB的功能丧失极其敏感。视网膜母细胞瘤发生于生命早期，并且在生殖系RB突变杂合子个体中发生率高，散发性视网膜母细胞瘤总是在PB基因中具有体细胞突变。相反，视网膜母细胞瘤不会在Rb+/-小鼠中发生。虽然视网膜母细胞瘤被认为具有发育起源，但Rb在视网膜发育中的功能尚未完全表征。在这里，我们研究了Rb在正常视网膜发育和视网膜母细胞瘤中的作用，使用条件性Rb突变的小鼠。在胚胎发育后期，Rb缺乏的视网膜表现出异位S期和高水平的p53非依赖性细胞凋亡，特别是在分化的视网膜神经节细胞层。在出生后的视网膜发育过程中，Rb的缺失导致更广泛的视网膜细胞凋亡，成年人表现出光感受器和双极细胞的缺失。视网膜中的条件性Rb突变即使在p53突变背景下也不会导致视网膜母细胞瘤的形成。然而，在p107或p130缺陷的背景下，视网膜中的Rb突变引起视网膜发育不良或视网膜母细胞瘤。
Certain cells of the human retina are extremely sensitive to loss of function of the retinoblastoma tumor suppressor gene RB. Retinoblastomas develop early in life and at high frequency in individuals heterozygous for a germ-line RB mutation, and sporadic retinoblastomas invariably have somatic mutation in the PB gene. In contrast, retinoblastomas do not develop in Rb+/- mice. Although retinoblastoma is thought to have developmental origins, the function of Rb in retinal development has not been fully characterized. Here we studied the role of Rb in normal retinal development and in retinoblastoma using conditional Rb mutations in the mouse. In late embryogenesis, Rb-deficient retinas exhibited ectopic S-phase and high levels of p53-independent apoptosis, particularly in the differentiating retinal ganglion cell layer. During postnatal retinal development, loss of Rb led to more widespread retinal apoptosis, and adults showed loss of photoreceptors and bipolar cells. Conditional Rb mutation in the retina did not result in retinoblastoma formation even in a p53-mutant background. However, on a p107- or p130-deficient background, Rb mutation in the retina caused retinal dysplasia or retinoblastoma.