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生长激素缺乏症的常见和罕见小鼠模型。

Common and Uncommon Mouse Models of Growth Hormone Deficiency.

机构信息

Edison Biotechnology Institute, Ohio University, Athens, OH 45701, USA.

Department of Specialty Medicine, Heritage College of Osteopathic Medicine, Athens, OH 45701, USA.

出版信息

Endocr Rev. 2024 Nov 22;45(6):818-842. doi: 10.1210/endrev/bnae017.

Abstract

Mouse models of growth hormone deficiency (GHD) have provided important tools for uncovering the various actions of GH. Nearly 100 years of research using these mouse lines has greatly enhanced our knowledge of the GH/IGF-1 axis. Some of the shared phenotypes of the 5 "common" mouse models of GHD include reduced body size, delayed sexual maturation, decreased fertility, reduced muscle mass, increased adiposity, and enhanced insulin sensitivity. Since these common mouse lines outlive their normal-sized littermates-and have protection from age-associated disease-they have become important fixtures in the aging field. On the other hand, the 12 "uncommon" mouse models of GHD described herein have tremendously divergent health outcomes ranging from beneficial aging phenotypes (similar to those described for the common models) to extremely detrimental features (such as improper development of the central nervous system, numerous sensory organ defects, and embryonic lethality). Moreover, advancements in next-generation sequencing technologies have led to the identification of an expanding array of genes that are recognized as causative agents to numerous rare syndromes with concomitant GHD. Accordingly, this review provides researchers with a comprehensive up-to-date collection of the common and uncommon mouse models of GHD that have been used to study various aspects of physiology and metabolism associated with multiple forms of GHD. For each mouse line presented, the closest comparable human syndromes are discussed providing important parallels to the clinic.

摘要

生长激素缺乏症(GHD)的小鼠模型为揭示 GH 的各种作用提供了重要工具。近 100 年来,使用这些小鼠系进行的研究极大地增强了我们对 GH/IGF-1 轴的认识。“常见”的 5 种 GHD 小鼠模型的一些共同表型包括体型减小、性成熟延迟、生育力下降、肌肉量减少、脂肪量增加和胰岛素敏感性增强。由于这些常见的小鼠系比其正常体型的同窝仔鼠寿命更长,并且免受与年龄相关疾病的影响,因此它们已成为衰老领域的重要研究对象。另一方面,本文所述的 12 种“不常见”的 GHD 小鼠模型具有极大不同的健康结果,从有益的衰老表型(类似于常见模型所描述的)到极其有害的特征(如中枢神经系统发育不当、多种感觉器官缺陷和胚胎致死性)。此外,下一代测序技术的进步导致了越来越多的基因被识别为导致多种伴有 GHD 的罕见综合征的原因。因此,本综述为研究人员提供了一个全面的、最新的 GHD 常见和罕见小鼠模型的集合,这些模型被用于研究与多种形式的 GHD 相关的生理学和代谢的各个方面。对于提出的每条小鼠系,都讨论了最接近的可比人类综合征,为临床提供了重要的平行。

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