Overexpression of p27Kip1 lengthens the G1 phase in a mouse model that targets inducible gene expression to central nervous system progenitor cells
Overexpression of p27Kip1 lengthens the G1 phase in a mouse model that targets inducible gene expression to central nervous system progenitor cells
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DOI：
10.1073/pnas.111051398
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发表时间：
2001-05-22
影响因子：
11.1
通讯作者：
Caviness, VS
中科院分区：
文献类型：
--
作者：
Mitsuhashi, T;Aoki, Y;Caviness, VS
我们描述了一种转基因表达p27(Kip1)的小鼠模型，在该模型中，p27(Kip1)的表达在空间上限于中枢神经系统神经上皮，并在时间上受多西环素的控制。在给予多西环素的6h内可检测到转基因特异性转录本，并在12h内达到最大非致死性表达，在转基因表达18-26h后，新皮质神经上皮细胞周期的G(1)期估计从9-13h增加，这是正常小鼠这种增殖群体所能达到的最大G(1)期长度。因此，我们的数据在哺乳动物中枢神经系统中建立了p27(Kip1)和控制G(1)期长度之间的直接联系，并揭示了尽管p27(Kip1)正在进行转基因表达，但将G(1)期长度限制在假定的生理最大值的内在机制。
We describe a mouse model in which p27(Kip1) transgene expression is spatially restricted to the central nervous system neuroepithelium and temporally controlled with doxycycline. Transgenespecific transcripts are detectable within 6 h of doxycycline administration, and maximum nonlethal expression is approached within 12 h, After 18-26 h of transgene expression, the G(1) phase of the cell cycle is estimated to increase from 9 to 13 h in the neocortical neuroepithelium, the maximum G(1) phase length attainable in this proliferative population in normal mice. Thus our data establish a direct link between p27(Kip1) and control of G(1) phase length in the mammalian central nervous system and unveil intrinsic mechanisms that constrain the G(1) phase length to a putative physiological maximum despite ongoing p27(Kip1) transgene expression.