Edison Biotechnology Institute, Ohio University, Athens, OH, USA.
Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, USA.
Pituitary. 2022 Feb;25(1):1-51. doi: 10.1007/s11102-021-01191-y. Epub 2021 Nov 19.
Much of our understanding of GH's action stems from animal models and the generation and characterization of genetically altered or modified mice. Manipulation of genes in the GH/IGF1 family in animals started in 1982 when the first GH transgenic mice were produced. Since then, multiple laboratories have altered mouse DNA to globally disrupt Gh, Ghr, and other genes upstream or downstream of GH or its receptor. The ability to stay current with the various genetically manipulated mouse lines within the realm of GH/IGF1 research has been daunting. As such, this review attempts to consolidate and summarize the literature related to the initial characterization of many of the known gene-manipulated mice relating to the actions of GH, PRL and IGF1. We have organized the mouse lines by modifications made to constituents of the GH/IGF1 family either upstream or downstream of GHR or to the GHR itself. Available data on the effect of altered gene expression on growth, GH/IGF1 levels, body composition, reproduction, diabetes, metabolism, cancer, and aging are summarized. For the ease of finding this information, key words are highlighted in bold throughout the main text for each mouse line and this information is summarized in Tables 1, 2, 3 and 4. Most importantly, the collective data derived from and reported for these mice have enhanced our understanding of GH action.
我们对 GH 作用的了解很大程度上源于动物模型,以及对基因发生改变或修饰的老鼠的生成和特征描述。1982 年,首次生产出 GH 转基因老鼠,自此开始在动物中对 GH/IGF1 家族的基因进行操作。此后,多个实验室改变了老鼠的 DNA,以全面破坏 GH、Ghr 和 GH 或其受体上下游的其他基因。要跟上 GH/IGF1 研究领域中各种基因修饰老鼠的研究步伐,是一项艰巨的任务。因此,本综述尝试整合和总结与 GH、PRL 和 IGF1 作用相关的许多已知基因修饰老鼠的初始特征的文献。我们根据对 GHR 上下游的 GH/IGF1 家族成分或 GHR 本身进行的修饰,对老鼠品系进行了组织。总结了改变基因表达对生长、GH/IGF1 水平、身体成分、繁殖、糖尿病、代谢、癌症和衰老的影响的相关数据。为了便于查找这些信息,本文中的每个老鼠品系的关键词都以粗体突出显示,相关信息总结在表 1、2、3 和 4 中。最重要的是,这些老鼠的数据的累积和报告增强了我们对 GH 作用的理解。