The conserved phosphoinositide 3-kinase pathway determines heart size in mice
The conserved phosphoinositide 3-kinase pathway determines heart size in mice
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DOI：
10.1093/emboj/19.11.2537
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发表时间：
2000-06-01
期刊：
影响因子：
11.4
通讯作者：
Izumo, S
中科院分区：
文献类型：
--
作者：
Shioi, T;Kang, PM;Izumo, S
磷酸肌醇 3-激酶 (PI3K) 已被证明可以调节果蝇的细胞和器官大小，但 PI3K 在脊椎动物体内的作用尚不清楚。为了研究 PI3K 在完整哺乳动物组织中的作用，我们创建并表征了在心脏中表达 PI3K 组成型活性或显性失活突变体的转基因小鼠。组成型活性 PI3K 的心脏特异性表达导致小鼠心脏较大，而显性失活 PI3K 导致小鼠心脏较小。心脏大小的增加或减少与心肌细胞大小的相当的增加或减少相关。在这两种小鼠中均未观察到心肌病变化，如心肌细胞坏死、细胞凋亡、间质纤维化或收缩功能障碍。 因此，PI3K途径对于促进哺乳动物器官生长是必要且充分的。
Phosphoinositide 3-kinase (PI3K) has been shown to regulate cell and organ size in Drosophila, but the role of PI3K in vertebrates in vivo is not well understood. To examine the role of PI3K in intact mammalian tissue, we have created and characterized transgenic mice expressing constitutively active or dominant-negative mutants of PI3K in the heart. Cardiac-specific expression of constitutively active PI3K resulted in mice with larger hearts, while dominant-negative PI3K resulted in mice with smaller hearts, The increase or decrease in heart size was associated with comparable increase or decrease in myocyte size, Cardiomyopathic changes, such as myocyte necrosis, apoptosis, interstitial fibrosis or contractile dysfunction, were not observed in either of the transgenic mice, Thus, the PI3K pathway is necessary and sufficient to promote organ growth in mammals.