Mouse models of growth hormone deficiency
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Mouse models of growth hormone deficiency Edward O. List 1,2
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Reetobrata Basu 1
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Silvana Duran-Ortiz 1
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Jackson Krejsa 1 & Elizabeth A. Jensen 1,2
Accepted: 1 October 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Nearly one century of research using growth hormone deficient (GHD) mouse lines has contributed greatly toward our knowledge of growth hormone (GH), a pituitary-derived hormone that binds and signals through the GH receptor and affects many metabolic processes throughout life. Although delayed sexual maturation, decreased fertility, reduced muscle mass, increased adiposity, small body size, and glucose intolerance appear to be among the negative characteristics of these GHD mouse lines, these mice still consistently outlive their normal sized littermates. Furthermore, the absence of GH action in these mouse lines leads to enhanced insulin sensitivity (likely due to the lack of GH’s diabetogenic actions), delayed onset for a number of ageassociated physiological declines (including cognition, cancer, and neuromusculoskeletal frailty), reduced cellular senescence, and ultimately, extended lifespan. In this review, we provide details about history, availability, growth, physiology, and aging of five commonly used GHD mouse lines. Keywords Growth hormone deficiency . Mouse models . Knockout mice . Ames mice . Snell mice . Lit/lit . GHRHKO . GHKO
1 Introduction Growth hormone (GH) is important in regulating numerous metabolic processes throughout the body, affecting most cell types. While GH is best known for its capability in stimulating growth during puberty, it has many other diverse physiological activities involved in regulating adiposity, glucose homeostasis, reproduction, and aging. To help elucidate the many actions of GH, mouse lines with GH deficiency (GHD) have been extensively utilized. While some of the first GHD mouse lines were “accidentally” discovered as small mice present in colonies among normal sized mice, more recent lines have been genetically engineered to provide researchers with valuable tools for uncovering the many actions of GH. This review will focus on five mouse lines commonly used in scientific research as genetic models of human GHD. Chronologically, the first of these GHD mouse lines to be described was the
* Edward O. List [email protected] 1
The Edison Biotechnology Institute, Ohio University, 172 Water Tower Drive, Athens, OH 45701, USA
2
The Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA
Snell dwarf mouse line in 1929 by George D. Snell [1] (Fig. 1). Snell mice have a W261C spontaneous point mutation in the pituitary-specific transcription factor-1 (Pit1) gene that results in multiple pituitary hormone deficiencies, including GH, prolactin (PRL), and thyroidstimulating hormone (TSH) (Table 1). Next, in 1961, the Ames dwarf mouse was described by Robert Schaible and J.W. Gowen [2]. Similar to Snell mice, Ames dwarf mice lack multiple pituitary hormones due t
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