EXPRESSION OF INSULIN-LIKE GROWTH FACTOR-I STIMULATES NORMAL SOMATIC GROWTH IN GROWTH HORMONE-DEFICIENT TRANSGENIC MICE
EXPRESSION OF INSULIN-LIKE GROWTH FACTOR-I STIMULATES NORMAL SOMATIC GROWTH IN GROWTH HORMONE-DEFICIENT TRANSGENIC MICE
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DOI：
10.1210/endo-127-3-1033
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发表时间：
1990-09-01
期刊：
影响因子：
4.8
通讯作者：
DERCOLE, AJ
中科院分区：
文献类型：
--
作者：
BEHRINGER, RR;LEWIN, TM;DERCOLE, AJ
将在小鼠金属硫蛋白-1启动子控制下表达胰岛素样生长因子-I (IGF-I) 的转基因小鼠系与缺乏 GH 表达细胞的侏儒转基因小鼠系杂交，这些细胞被白喉毒素表达基因消除。由该杂交产生的携带两种转基因的小鼠在缺乏 GH 的情况下表达 IGF-I。这些小鼠比其缺乏 GH 的转基因同窝小鼠长得更大，并且其体重和线性生长与其非转基因小鼠没有区别。这些结果证实了IGF-I在介导GH对体细胞生长（包括长骨的生长）的刺激中的可疑作用，并说明了GH和IGF-I在调节出生后生长中的重要作用。然而，对这些小鼠器官生长差异的分析表明，GH 和 IGF-I 也具有彼此独立的生长促进作用； GH 似乎是获得正常肝脏大小所必需的，而 IGF-I 可以刺激大脑生长。
A line of transgenic mice expressing insulin-like growth factor-I (IGF-I) under the control of the mouse metalothionien-1 promoter was crossed to a line of dwarf transgenic mice lacking GH expressing cells that were genetically ablated by diphtheria toxin expression. Mice generated from this cross that carry both transgenes express IGF-I in the absence of GH. These mice grew larger than their GH-deficient transgenic littermates and exhibited weight and linear growth indistinguishable from that of their nontransgenic siblings. These results confirm the suspected role of IGF-I in mediating GH''s stimulation of somatic growth, including that of long bones, and illustrates the essential role of GH and IGF-I in the modulation of postnatal growth. Analysis of differences in organ growth among these mice, however, suggests that GH and IGF-I also have growth promoting actions that are independent of one another; GH appears to be necessary for the attainment of normal liver size, while IGF-I can stimulate brain growth.