The transcription factor Stat3 is dispensable for pancreatic β-cell development and function
The transcription factor Stat3 is dispensable for pancreatic β-cell development and function
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DOI：
10.1016/j.bbrc.2005.06.162
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发表时间：
2005-09-02
影响因子：
3.1
通讯作者：
Hennighausen, L
中科院分区：
文献类型：
--
作者：
Lee, JY;Hennighausen, L
转录因子Stat 3被多种细胞因子激活，包括瘦素和通过gp 130受体进行信号传导的细胞因子。在两项独立的研究中，使用RIP-Cre转基因使Stat 3基因失活的小鼠导致葡萄糖耐受不良、早期胰岛素分泌缺陷和轻度肥胖[S.五郎川，Y. Fujitani，H. Kaneto，Y. Hazama，H. Watada，Y. Miyamoto，K. Takeda，S. Akira，M. Magnuson，Y.山崎山Kajimoto，M. Hori，胰腺β细胞特异性STAT 3敲除小鼠中的胰岛素分泌缺陷和受损的胰岛结构，Biochem. Biophys.通信资源319（2004）1159; Y.崔湖，加-地Huang，F.埃莱夫特里乌湾杨，J.谢尔顿，J.贾尔斯，O.奥兹，T。普尔巴赫拉米角Lu，J. Richardson，G.卡森蒂角Li，Essential role of STAT3 in body weight and glucose homeostasis，Mol. Cell. 24（2004）258]。然而，由于RIP-Cre转基因也在下丘脑中表达，因此Stat 3从表达瘦素受体的神经元中缺失，因此不清楚哪种代谢缺陷是由于β细胞或下丘脑中Stat 3的缺失。我们已经通过使用Pdx 1-Cre转基因使胰腺β细胞中的Stat 3失活来解决这个问题。在来自小鼠的胰岛中观察到Stat 3的完全丢失，所述小鼠携带两个（foxed Stat 3等位基因和Pdx 1-Cre转基因。然而，这些小鼠在6个月的时间内没有发生葡萄糖耐受不良或肥胖，这表明Stat 3对于β细胞的产生和生理学是有益的。类似地，仅表达Pdx 1-Cre转基因的小鼠表现出正常的生理机能。相比之下，仅表达RIP-Cre转基因的小鼠早在6周龄时就出现了葡萄糖耐受不良。RIP-Cre转基因小鼠在C57 B/6占主导地位的背景下发展葡萄糖耐受不良的发现是重要的，因为该品系已用于几项研究。爱思唯尔公司出版
The transcription factor Stat3 is activated by multiple cytokines, including leptin and those signaling through the gp130 receptor. In two independent studies, mice in which the Stat3 gene was inactivated using a RIP-Cre transgene led to glucose intolerance, defects in early-phase insulin secretion, and mild obesity [S. Gorogawa, Y. Fujitani, H. Kaneto, Y. Hazama, H. Watada, Y. Miyamoto, K. Takeda, S. Akira, M. Magnuson, Y. Yamasaki, Y. Kajimoto, M. Hori, Insulin secretory defects and impaired islet architecture in pancreatic beta-cell-specific STAT3 knockout mice, Biochem. Biophys. Res. Commun. 319 (2004) 1159; Y. Cui, L. Huang, F. Elefteriou, G. Yang, J. Shelton, J. Giles, O. Oz, T. Pourbahrami, C. Lu, J. Richardson, G. Karsenty, C. Li, Essential role of STAT3 in body weight and glucose homeostasis, Mol. Cell. Biol. 24 (2004) 258]. However, since the RIP-Cre transgene is also expressed in the hypothalamus, and thereby Stat3 was deleted from neurons expressing the leptin receptor, it was not clear as to which of the metabolic defects were due to the loss of Stat3 from beta-cells or the hypothalamus. We have addressed this issue through the inactivation of Stat3 from pancreatic (3-cells using a Pdx1-Cre transgene. Complete loss of Stat3 was observed in islets from mice, which carry two (foxed Stat3 alleles and the Pdx1-Cre transgene. However, these mice did not develop glucose intolerance or obesity over a period of 6 months, demonstrating that Stat3 is dispensable for the generation and physiology of beta-cells. Similarly, mice that express only the Pdx1-Cre transgene display a normal physiology. In contrast, mice that expressed only the RIP-Cre transgene developed glucose intolerance as early as 6 weeks of age. The finding that RIP-Cre transgenic mice in a C57B/6 dominated background develop glucose intolerance is important as this line has been used in several studies. Published by Elsevier Inc.