Pomp D, Oberbauer A M, Murray J D
Department of Animal Science, Oklahoma State University, Stillwater 74078, USA.
Transgenic Res. 1996 Jan;5(1):13-23. doi: 10.1007/BF01979918.
Mice with a temporally regulatable ovine metallothionein 1a--ovine growth hormone transgene (oMT1a-oGH) were utilized to study the effects of withdrawal of elevated circulating levels of growth hormone (GH) on growth and body composition. The transgene was activated from 21-42 days of age by provision of zinc sulfate in the drinking water. At 42 days, mice were allocated to either activated transgenic (remain on zinc sulfate) or inactivated transgenic (removal of zinc sulfate) groups, and to receive either ad libitum or restricted (80-90% of ad libitum) access to feed. Non-transgenic control mice were treated similarly. Body weights and intakes were recorded weekly. Mice were killed at 70 d and epididymal and subcutaneous fat pads, trimmed hind carcass and various organs were weighed. The main findings of this study are: (1) food-restricted mice possessing an activated oMT1a-oGH transgene fail to demonstrate increased growth, but exhibit significantly reduced levels of fat (P < 0.05) relative to all other genotype x feed level combinations; and (2) inactivation of the oMT1a-oGH transgene, following a period of elevated GH levels, leads to development of obesity as evidenced by two to three fold increases in epididymal and subcutaneous fat pad weights (P < 0.01) relative to both activated transgenic and non-transgenic control mice. These large increases in fat deposition also occurred when intake was restricted to 80-90% of ad libitum levels, indicating that metabolic changes independent of intake occur in these inactivated transgenic mice. It is possible that highly elevated production of GH in activated oMT1a-oGH transgenic mice leads to (1) enhanced promotion of preadipocyte differentiation, leading to increased numbers of adipocytes that, upon cessation of oGH production, are available for lipid deposition resulting in obesity, or (2) alterations in production of or responsiveness to insulin, leading to increased fat deposition upon removal of the chronic anti-lipogenic actions of GH. The oMT1a-oGH transgenic mouse line should provide a new genetic model with which to investigate the mechanisms by which growth hormone affects obesity.
利用具有时间可调控的绵羊金属硫蛋白1a-绵羊生长激素转基因（oMT1a-oGH）的小鼠，研究循环生长激素（GH）水平升高后其撤除对生长和身体组成的影响。在21至42日龄时，通过在饮用水中添加硫酸锌来激活转基因。42日龄时，将小鼠分为激活转基因组（继续饮用含硫酸锌的水）或失活转基因组（去除硫酸锌），并给予自由采食或限食（自由采食量的80-90%）。非转基因对照小鼠也进行类似处理。每周记录体重和采食量。70日龄时处死小鼠，称量附睾和皮下脂肪垫、修剪后的后躯胴体及各种器官的重量。本研究的主要发现如下：（1）具有激活的oMT1a-oGH转基因的限食小鼠未表现出生长增加，但相对于所有其他基因型×饲料水平组合，其脂肪水平显著降低（P<0.05）；（2）在GH水平升高一段时间后，oMT1a-oGH转基因失活导致肥胖的发生，附睾和皮下脂肪垫重量相对于激活转基因小鼠和非转基因对照小鼠增加了两到三倍（P<0.01）。当采食量限制在自由采食量的80-90%时，脂肪沉积也有大幅增加，表明这些失活转基因小鼠发生了与采食量无关的代谢变化。激活的oMT1a-oGH转基因小鼠中GH的高产量可能导致：（1）促进前脂肪细胞分化增强，导致脂肪细胞数量增加，在停止产生oGH后，这些脂肪细胞可用于脂质沉积，从而导致肥胖；或（2）胰岛素产生或反应性改变，在去除GH的慢性抗脂肪生成作用后导致脂肪沉积增加。oMT1a-oGH转基因小鼠品系应能提供一个新的遗传模型，用以研究生长激素影响肥胖的机制。
