Mouse models of growth hormone insensitivity
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Mouse models of growth hormone insensitivity Jonathan Young 1,2
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Stephen Bell 1,2
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Yanrong Qian 2
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Caroline Hyman 1
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Darlene E. Berryman 1,2
Accepted: 1 October 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Growth hormone (GH) induces pleiotropic effects on growth and metabolism via binding and subsequent activation of the growth hormone receptor (GHR) and its downstream signaling pathways. Growth hormone insensitivity (GHI) describes a group of disorders in which there is resistance to the action of GH and resultant insulin-like growth factor I (IGF-I) deficiency. GHI is commonly due to genetic disorders of the GH receptor causing GH receptor deficiency (e.g. Laron Syndrome (LS)), decreased activation of GHR, or defects in post-receptor signaling molecules. Genetically altered mouse lines have been invaluable to better understand the physiological impact of GHI due to the ability to do invasive and longitudinal measures of metabolism, growth, and health on a whole animal or in individual tissues/cells. In the current review, the phenotype of mouse lines with GHI will be reviewed. Mouse lines to be discussed include: 1) GHR−/− mice with a gene disruption in the GHR that results in no functional GHR throughout life, also referred to as the Laron mouse, 2) mice with temporal loss of GHR (aGHRKO) starting at 6 weeks of age, 3) mice transgenic for a GHR antagonist (GHA mice), 4) mice with GHI in select tissues or cells generated via Cre-lox or related technology, and 5) assorted mice with defects in post-receptor signaling molecules. Collectively, these mouse lines have revealed an intriguing role of GH action in health, disease, and aging. Keywords Growth hormone . Mouse lines . Growth hormone insensitivity . Growth hormone resistance . GHR-/- mice . GHA mice
1 Introduction Understanding the function of hormones and how they may contribute to the metabolic or physiologic processes of complex systems requires in vivo models. That is, hormones affect multiple organs simultaneously; thus, in vivo mammalian models provide specific advantages over in vitro models, which are limited to investigation of isolated systems. To that end, genetically engineered mice have played a vital role in our understanding of many hormones due to their ease in genetic tractability, shorter lifespan, and genetic similarity to humans. ‘Transgenic animals’ that carry a foreign or overexpressed gene and ‘knockout mice’ in which the expression of a particular gene is disrupted globally, temporally or tissuespecifically can yield valuable information about the physiological or metabolic function of that protein. * Darlene E. Berryman [email protected] 1
Department of Biomedical Sciences, Ohio University Heritage College of Osteopathic Medicine, Athens, OH 45701, USA
2
Edison Biotechnology Institute, Konneker Research Labs, Ohio University, Athens, OH, USA
Many mouse lines with alterations in GH action have been generated and have uncovered novel roles for GH. In the current review, we will di
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