Jiang Z, Liang P, Leng R, Guo Z, Liu Y, Liu X, Bubnic S, Keating A, Murray D, Goss P, Zacksenhaus E
Department of Medicine, Toronto General Hospital Research Institute, University Health Network, University of Toronto, 67 College Street, Toronto, Ontario, Canada.
Dev Biol. 2000 Nov 1;227(1):8-41. doi: 10.1006/dbio.2000.9892.
We describe temporal and genetic analyses of partially rescued Rb mutant fetuses, mgRb:Rb-/-, that survive to birth and reveal specific defects in skeletal muscle differentiation. We show that in the absence of Rb, these fetuses exhibit increased apoptosis, bona fide endoreduplication, and incomplete differentiation throughout terminal myogenesis. These defects were further augmented in composite mutant fetuses, mgRb:Rb-/-:p21-/-, lacking both Rb and the cyclin-dependent kinase inhibitor p21(Waf1/Cip1). Although E2F1 and p53 mediate ectopic DNA synthesis and cell death in several tissues in Rb mutant embryos, both endoreduplication and apoptosis persisted in mgRb:Rb-/-:E2F1-/- and mgRb:Rb-/-:p53-/- compound mutant muscles. Thus, combined inactivation of Rb and p21(Waf1/Cip1) augments endoreduplication and apoptosis, whereas E2F1 and p53 are dispensable during aberrant myogenesis in Rb-deficient fetuses.
我们描述了部分挽救的 Rb 突变胎儿（mgRb:Rb-/-）的时间和遗传分析，这些胎儿能存活至出生，并揭示了骨骼肌分化中的特定缺陷。我们发现，在缺乏 Rb 的情况下，这些胎儿在整个终末肌生成过程中表现出凋亡增加、真正的核内复制以及不完全分化。在同时缺乏 Rb 和细胞周期蛋白依赖性激酶抑制剂 p21（Waf1/Cip1）的复合突变胎儿（mgRb:Rb-/-:p21-/-）中，这些缺陷进一步加剧。尽管 E2F1 和 p53 在 Rb 突变胚胎的多个组织中介导异位 DNA 合成和细胞死亡，但核内复制和凋亡在 mgRb:Rb-/-:E2F1-/- 和 mgRb:Rb-/-:p53-/- 复合突变肌肉中仍然存在。因此，Rb 和 p21（Waf1/Cip1）的联合失活增强了核内复制和凋亡，而在 Rb 缺陷胎儿的异常肌生成过程中，E2F1 和 p53 是可有可无的。
