IN-VIVO VIABILITY OF POSTMITOTIC PURKINJE NEURONS REQUIRES PRB FAMILY MEMBER FUNCTION
IN-VIVO VIABILITY OF POSTMITOTIC PURKINJE NEURONS REQUIRES PRB FAMILY MEMBER FUNCTION
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DOI：
10.1006/mcne.1995.1014
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发表时间：
1995-04-01
影响因子：
3.5
通讯作者：
ORR, HT
中科院分区：
文献类型：
--
作者：
FEDDERSEN, RM;CLARK, HB;ORR, HT
已知视网膜母细胞瘤易感基因 pRb 的产物是细胞分裂的重要调节因子。 Pa缺失小鼠中枢神经系统发育中断表明pRb在某些神经元的增殖停滞和终末分化启动中具有关键功能。此前，我们已经证明，转基因小鼠中针对浦肯野神经元的 SV40 T-ag 表达会导致细胞特异性死亡。在这里，我们描述了标签表达诱导 DNA 合成并导致浦肯野神经元中的 DNA 片段化。表达突变 T-ag 的转基因小鼠系的表征表明，T-ag 的 pRb 结合域是诱导浦肯野细胞损失所必需的。这些发现表明，pRb 功能在浦肯野神经元分化完成之后是必需的，并提供了体内细胞周期调节和神经变性之间的联系。 (C) 1995 学术出版社
The product of the retinoblastoma susceptibility gene, pRb, is known to be an important regulator of cell division. Disrupted central nervous system development in Pa null mice suggests a critical function for pRb in the proliferative arrest and initiation of terminal differentiation of certain neurons. Previously, we have shown that SV40 T-ag expression targeted to Purkinje neurons in transgenic mice causes cell-specific death. Here we describe that Tag expression induces DNA synthesis and results in DNA fragmentation in Purkinje neurons. Characterization of transgenic mouse lines expressing mutant T-ags demonstrate that the pRb binding domain of T-ag is required for induction of Purkinje cell loss. These findings indicate that a pRb function is required well beyond the completion of Purkinje neuron differentiation and provide a link between cell cycle regulation and neurodegeneration in vivo. (C) 1995 Academic Press, Inc.