Transgenic mice overexpressing des-acyl ghrelin show small phenotype
Transgenic mice overexpressing des-acyl ghrelin show small phenotype
复制标题
DOI：
10.1210/en.2004-0629
复制
发表时间：
2005-01-01
期刊：
影响因子：
4.8
通讯作者：
Nakao, K
中科院分区：
文献类型：
--
作者：
Ariyasu, H;Takaya, K;Nakao, K
Ghrelin 是一种 28 个氨基酸酰化肽，与 GHRH 协同作用，表现出强烈的 GH 释放活性。生长素释放肽的脂肪酸修饰对于其作用至关重要，而缺乏修饰的去酰基生长素释放肽被认为没有生物效应。然而，最近的一些报告表明去酰基生长素释放肽对细胞增殖和存活有影响。在本研究中，我们产生了两个转基因小鼠品系，它们携带受鸡β-肌动蛋白启动子控制的前饥饿素原基因。转基因小鼠在多种组织中过度表达去酰基生长素释放肽，血浆去酰基生长素释放肽水平分别达到对照小鼠的 10 倍和 44 倍。与对照组小鼠相比，它们的体重更轻，鼻子到肛门的长度更短。与对照小鼠相比，雄性和雌性转基因小鼠的血清GH水平趋于较低，且血清IGF-I水平显着较低。与对照小鼠相比，GH 对 GHRH 的反应正常，而对 ghrelin 的反应降低，尤其是雌性转基因小鼠。这些数据表明，过表达的去酰基生长素释放肽可能调节 GH-IGF-I 轴并导致转基因小鼠出现较小的表型。
Ghrelin, a 28-amino acid acylated peptide, displays strong GH-releasing activity in concert with GHRH. The fatty acid modification of ghrelin is essential for the actions, and desacyl ghrelin, which lacks the modification, has been assumed to be devoid of biological effects. Some recent reports, however, indicate that des-acyl ghrelin has effects on cell proliferation and survival. In the present study, we generated two lines of transgenic mice bearing the preproghrelin gene under the control of chicken beta-actin promoter. Transgenic mice overexpressed des-acyl ghrelin in a wide variety of tissues, and plasma des-acyl ghrelin levels reached 10- and 44-fold of those in control mice. They exhibited lower body weights and shorter nose-to-anus lengths, compared with control mice. The serum GH levels tended to be lower, and the serum IGF-I levels were significantly lower in both male and female transgenic mice than control mice. The responses of GH to administered GHRH were normal, whereas those to administered ghrelin were reduced, especially in female transgenic mice, compared with control mice. These data suggest that overexpressed des-acyl ghrelin may modulate the GH-IGF-I axis and result in small phenotype in transgenic mice.