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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Mutation of p107 exacerbates the consequences of Rb loss in embryonic tissues and causes cardiac and blood vessel defects
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Mutation of p107 exacerbates the consequences of Rb loss in embryonic tissues and causes cardiac and blood vessel defects

机译：p107突变加剧了胚胎组织中Rb丢失的后果，并导致心脏和血管缺陷

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摘要

The retinoblastoma tumor-suppressor protein, pRb, is a member of the pocket protein family that includes p107 and p130. These proteins have well-defined roles in regulating entry into and exit from the cell cycle and also have cell cycle-independent roles in facilitating differentiation. Here we investigate the overlap between pocket protein's function during embryonic development by using conditional mutant alleles to generate Rb;p107 double-mutant embryos (DKOs) that develop in the absence of placental defects. These DKOs die between e13.5 and e14.5, much earlier than either the conditional Rb or the germline p107 single mutants, which survive to birth or are largely viable, respectively. Analyses of the e13.5 DKOs shows that p107 mutation exacerbates the phenotypes resulting from pRb loss in the central nervous system and lens, but not in the peripheral nervous system. In addition, these embryos exhibit novel phenotypes, including increased proliferation of blood vessel endothelial cells, and heart defects, including double-outlet right ventricle (DORV). The DORV is caused, at least in part, by a defect in blood vessel endothelial cells and/or heart mesenchymal cells. These findings demonstrate novel, overlapping functions for pRb and p107 in numerous murine tissues.
机译：视网膜母细胞瘤肿瘤抑制蛋白pRb是口袋蛋白家族的成员，其中包括p107和p130。这些蛋白质在调节进入和退出细胞周期中具有明确定义的作用，并且在促进分化中也具有非细胞周期独立的作用。在这里，我们通过使用条件突变等位基因来生成在无胎盘缺陷的情况下发育的Rb; p107双突变胚胎（DKO），来研究口袋蛋白在胚胎发育过程中的功能重叠。这些DKO在e13.5和e14.5之间死亡，比有条件的Rb或生殖系p107单突变体早得多，后者分别存活到出生或在很大程度上存活。对e13.5 DKO的分析表明，p107突变加剧了中枢神经系统和晶状体中pRb丢失而导致的表型，但在周围神经系统中则没有。另外，这些胚胎表现出新的表型，包括增加的血管内皮细胞增殖，以及心脏缺陷，包括双出口右心室（DORV）。 DORV至少部分地由血管内皮细胞和/或心脏间充质细胞的缺陷引起。这些发现证明了pRb和p107在许多鼠类组织中具有新颖的重叠功能。

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