Common and Uncommon Mouse Models of Growth Hormone Deficiency

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.

Keywords: combined pituitary hormone deficiency; growth hormone deficiency; isolated growth hormone deficiency; knockout mice; mouse model.

Graphical Abstract

Figure 1.

Timeline of when each mouse model of growth hormone deficiency was first generated. Orange text indicates genetically engineered mouse lines, blue text indicates mouse lines discovered with spontaneous mutations, and red text indicates physical disruption of the pituitary.

Figure 2.

Targeting genes involved in pituitary development or growth hormone (GH) production to generate mouse models of GH deficiency (GHD). Targeting genes involved in pituitary development or GH production to generate mouse models of GHD. Most of the mouse models of GHD result from disruptions to genes with known roles in pituitary development or GH production and are listed in black.