生长激素受体基因敲除小鼠模型

Overview of growth hormone receptor knockout mouse models

由脑垂体合成并分泌的生长激素(GH)不仅控制机体生长发育,还在许多代谢疾病中起关键调控作用。GH的生物学功能通过与其表面受体(GHR)结合而启动,基于分子生物学技术构建各种GHR敲除小鼠模型成为揭示GH调控机制的基础。利用Cre-LoxP重组酶系统,迄今已在小鼠全身或组织特异性(如肝,骨骼肌,脂肪,巨噬细胞和胰岛β细胞等)敲除ghr基因,并从中探索GH/GHR信号转导及其与其他信号通路的相互作用。本文综述并讨论了这些ghr基因敲除小鼠模型的表型特征和应用,从不同方面介绍了GH/GHR相关信号通路研究现状。

Growth hormone(GH)is synthesized and released by somatotrophic cells in the pituitary gland.As well as functions in growth and development,GH is also important in many metabolic diseases.The biological functions of GH are initiated by ligand binding to the surface receptor,growth hormone receptor(GHR).Rapid advances in molecular technology have enabled construction of various GHR knockout mice models to examine the mechanisms of action of GH.Using a Cre-LoxP recombinase system,the mouse GHR has also been successfully knocked out systemically and tissue-specifically,including in the liver,skeletal muscle,adipose tissues,macrophages,and pancreatic isletβ-cells.This has provided a unique platform for studying GH/GHR signal transduction and its interactions with other signaling pathways.In this brief review,we discuss the phenotypic characteristics and applications of these GHR knockout mouse models.