Targeted disruption of p107: Functional overlap between p107 and Rb
Targeted disruption of p107: Functional overlap between p107 and Rb
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DOI：
10.1101/gad.10.13.1621
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发表时间：
1996-07-01
影响因子：
10.5
通讯作者：
Jacks, T
中科院分区：
文献类型：
--
作者：
Lee, MH;Williams, BO;Jacks, T
为了探索视网膜母细胞瘤基因（Rb）家族成员p107的生理作用，我们在胚胎干细胞中通过同源重组破坏小鼠基因。P107纯合子突变小鼠存活，可育，无明显异常。为了研究p107和Rb之间可能的功能重叠，产生了两个位点都发生突变的小鼠。Rb - + / -;P107（-/-）小鼠在出生后的前3周有明显的生长迟缓和死亡率增加。Rb - + / -;与Rb-+/-小鼠相比，存活至成年的p107（-/-）幼崽没有表现出任何肿瘤易感改变，但出现了多发性视网膜发育不良病变。Rb和p107纯合子的胚胎在妊娠11.5 d时死亡，比单独Rb纯合子的胚胎早2 d。组织学检查显示Rb- /-在肝脏和中枢神经系统加速凋亡；p107（-/-）胚胎相对于Rb- /-胚胎。这些结果首次提供了p107和Rb在发育和成年小鼠的某些组织中具有重叠功能的体内证据。
To explore the physiological role of p107, a member of retinoblastoma gene (Rb) family, we disrupted the mouse gene by homologous recombination in embryonic stem cells. p107 homozygous mutant mice were viable, fertile, and displayed no obvious abnormalities. To investigate possible functional overlap between p107 and Rb, mice with mutations at both loci were generated. Rb-+/-;p107(-/-) mice have a pronounced growth retardation and increased mortality rate during the first 3 weeks after birth. The Rb-+/-;p107(-/-) pups that survive to adulthood did not show any altered tumor predisposition when compared with Rb-+/- mice but developed multiple dysplastic lesions of the retina. Embryos homozygous for both Rb and p107 died at similar to 11.5 days of gestation, 2 days earlier than embryos homozygous for Rb alone. Histological examination revealed accelerated apoptosis in the liver and the central nervous system of Rb--/-;p107(-/-) embryos relative to Rb--/- embryos. These results provide the first in vivo evidence that p107 and Rb have overlapping functions in some tissues of the developing and adult mouse.