Growth retardation and increased apoptosis in mice with homozygous disruption of the akt1 gene
Growth retardation and increased apoptosis in mice with homozygous disruption of the akt1 gene
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DOI：
10.1101/gad.913901
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发表时间：
2001-09-01
影响因子：
10.5
通讯作者：
Hay, N
中科院分区：
文献类型：
--
作者：
Chen, WS;Xu, PZ;Hay, N
丝氨酸/苏氨酸激酶Akt与细胞存活和代谢的控制有关。在这里，我们报告的中断最普遍表达的成员akt家族的基因，akt 1，在小鼠中。Akt 1（-/-）小鼠是可行的，但与野生型同窝仔相比较小。此外，暴露于遗传毒性应激后，Akt 1（-/-）小鼠的寿命较短。然而，Akt 1（-/-）小鼠不显示糖尿病表型。在Akt 1（-/-）雄性小鼠中观察到睾丸自发性细胞凋亡增加和精子发生减弱。在Akt 1（-/-）小鼠胸腺中也观察到自发性凋亡增加，并且Akt 1（-/-）胸腺细胞对γ射线和地塞米松诱导的凋亡更敏感。最后，Akt 1（-/-）小鼠胚胎成纤维细胞（MEFs）对TNF、抗Fas抗体、紫外线照射和血清戒断诱导的凋亡更敏感。
The serine/threonine kinase Akt has been implicated in the control of cell survival and metabolism. Here we report the disruption of the most ubiquitously expressed member of the akt family of genes, akt1, in the mouse. Akt1(-/-) mice are viable but smaller when compared to wild-type littermates. In addition, the life span of Akt1(-/-) mice, upon exposure to genotoxic stress, is shorter. However, Akt1(-/-) mice do not display a diabetic phenotype. Increased spontaneous apoptosis in testes, and attenuation of spermatogenesis is observed in Akt1(-/-) male mice. Increased spontaneous apoptosis is also observed in the thymi of Akt1(-/-) mice, and Akt1(-/-)thymocytes are more sensitive to apoptosis induced by gamma -irradiation and dexamethasone. Finally, Akt1(-/-)mouse embryo fibroblasts (MEFs) are mote susceptible to apoptosis induced by TNF, anti-Fas, UV irradiation, and serum withdrawal.