Insights from insulin-like growth factor binding protein transgenic mice.
Insights from insulin-like growth factor binding protein transgenic mice.
复制标题
来自胰岛素样生长因子结合蛋白转基因小鼠的见解。
作者：
J. Silha;L. Murphy
胰岛素样生长因子结合蛋白(IGFBPs)存在着丰富的高亲和力结合蛋白，这是40多年前生长抑素研究的早期发现的。随着分子技术和转基因和基因敲除小鼠模型的发展，IGFBPs的性质、复杂性和冗余性现在已经开始被阐明。事实上，循环IGFS的功能作用和最初提出的内分泌生长抑素假说最近受到了质疑。迄今为止有限的报告表明IGFBP基因敲除小鼠几乎没有表型表现。相反，转基因小鼠中IGFBPs的过度表达与提供了对结合蛋白的生理作用的一些洞察的表现有关。IGFBPs的全身性或组织特异性过表达的主要作用是抑制生长，从抑制IGF-I和-II的作用可以预见到这一点。此外，在IGFBP-1和IGFBP-3过表达的转基因小鼠中都观察到了葡萄糖动态平衡受损和生殖力下降。这篇综述检查了迄今为止报告的过表达IGFBPs的转基因小鼠模型的数据。此外，来自过表达三元复合体重要组成部分不稳定酸亚单位的转基因小鼠的数据也已被综述。
The existence of abundant high affinity binding proteins for the IGFs, the IGF binding proteins (IGFBPs), was first demonstrated more than 40 yr ago in the very early days of somatomedin research. With the development of molecular techniques and transgenic and knockout mouse models, the nature, complexity, and redundancy of the IGFBPs have now started to be elucidated. Indeed the functional role of the circulating IGFs and the originally proposed endocrine somatomedin hypothesis have recently been questioned. The limited reports to date indicate that IGFBP knockout mice have few phenotypic manifestations. In contrast, overexpression of IGFBPs in transgenic mice is associated with manifestations that provide some insight into the physiological role of the binding proteins. The predominant effect of generalized or tissue-specific overexpression of the IGFBPs has been growth inhibition as would be anticipated from inhibition of the actions of IGF-I and -II. In addition, impaired glucose homeostasis and reduced fecundity have been observed in both IGFBP-1- and IGFBP-3-overexpressing transgenic mice. This review examines the data reported to date for transgenic mouse models that overexpress IGFBPs. In addition, data from transgenic mice that overexpress the acid-labile subunit, an important component of the ternary complex, have also been reviewed.