Growth Hormone Receptor Gene Disruption

Overview

Journal Vitam Horm

Specialties Endocrinology
Nutritional Sciences

Date 2023 Sep 17

PMID 37717983

Authors

Edward O List

Silvana Duran-Ortiz

Prateek Kulkarni

Emily Davis

Patricia Mora-Criollo

Darlene E Berryman

John J Kopchick

Affiliations

Soon will be listed here.

Abstract

Much of our understanding of growth hormone's (GH)'s numerous activities stems from studies utilizing GH receptor (GHR) knockout mice. More recently, the role of GH action has been examined by creating mice with tissue-specific or temporal GHR disruption. To date, 37 distinct GHR knockout mouse lines have been created. Targeted tissues include fat, liver, muscle, heart, bone, brain, macrophage, intestine, hematopoietic stem cells, pancreatic β cells, and inducible multi-tissue "global" disruption at various ages. In this chapter, a summary of each mouse line is provided with background information on the generation of the mouse line as well as important physiological outcomes resulting from GHR gene disruption. Collectively, these mouse lines provide unique insights into GH action and have resulted in the development of new hypotheses about the functions ascribed to GH action in particular tissues.

References

Li Y, Knapp J, Kopchick J . Enlargement of interscapular brown adipose tissue in growth hormone antagonist transgenic and in growth hormone receptor gene-disrupted dwarf mice. Exp Biol Med (Maywood). 2003; 228(2):207-15. DOI: 10.1177/153537020322800212. View

Fang F, Shi X, Brown M, Goldstein J, Liang G . Growth hormone acts on liver to stimulate autophagy, support glucose production, and preserve blood glucose in chronically starved mice. Proc Natl Acad Sci U S A. 2019; 116(15):7449-7454. PMC: 6462072. DOI: 10.1073/pnas.1901867116. View

Zhou Y, Xu B, Maheshwari H, He L, Reed M, Lozykowski M . A mammalian model for Laron syndrome produced by targeted disruption of the mouse growth hormone receptor/binding protein gene (the Laron mouse). Proc Natl Acad Sci U S A. 1997; 94(24):13215-20. PMC: 24289. DOI: 10.1073/pnas.94.24.13215. View

Cordoba-Chacon J, Majumdar N, List E, Diaz-Ruiz A, Frank S, Manzano A . Growth Hormone Inhibits Hepatic De Novo Lipogenesis in Adult Mice. Diabetes. 2015; 64(9):3093-103. PMC: 4542445. DOI: 10.2337/db15-0370. View

Zhang X, Mehta R, Lantvit D, Coschigano K, Kopchick J, Green J . Inhibition of estrogen-independent mammary carcinogenesis by disruption of growth hormone signaling. Carcinogenesis. 2006; 28(1):143-50. DOI: 10.1093/carcin/bgl138. View

Salmon A, Murakami S, Bartke A, Kopchick J, Yasumura K, Miller R . Fibroblast cell lines from young adult mice of long-lived mutant strains are resistant to multiple forms of stress. Am J Physiol Endocrinol Metab. 2005; 289(1):E23-9. DOI: 10.1152/ajpendo.00575.2004. View

Guo Y, Lu Y, Houle D, Robertson K, Tang Z, Kopchick J . Pancreatic islet-specific expression of an insulin-like growth factor-I transgene compensates islet cell growth in growth hormone receptor gene-deficient mice. Endocrinology. 2005; 146(6):2602-9. DOI: 10.1210/en.2004-1203. View

Lu C, Anil Kumar P, Sun J, Aggarwal A, Fan Y, Sperling M . Targeted deletion of growth hormone (GH) receptor in macrophage reveals novel osteopontin-mediated effects of GH on glucose homeostasis and insulin sensitivity in diet-induced obesity. J Biol Chem. 2013; 288(22):15725-35. PMC: 3668731. DOI: 10.1074/jbc.M113.460212. View

A Al-Regaiey K, Masternak M, Bonkowski M, Panici J, Kopchick J, Bartke A . Effects of caloric restriction and growth hormone resistance on insulin-related intermediates in the skeletal muscle. J Gerontol A Biol Sci Med Sci. 2007; 62(1):18-26. DOI: 10.1093/gerona/62.1.18. View

10.

Fan Y, Fang X, Tajima A, Geng X, Ranganathan S, Dong H . Evolution of hepatic steatosis to fibrosis and adenoma formation in liver-specific growth hormone receptor knockout mice. Front Endocrinol (Lausanne). 2015; 5:218. PMC: 4270248. DOI: 10.3389/fendo.2014.00218. View

11.

List E, Coschigano K, Kopchick J . Growth hormone receptor/binding protein (GHR/BP) knockout mice: a 3-year update. Mol Genet Metab. 2001; 73(1):1-10. DOI: 10.1006/mgme.2001.3164. View

12.

Lee K, Russell S, Ussar S, Boucher J, Vernochet C, Mori M . Lessons on conditional gene targeting in mouse adipose tissue. Diabetes. 2013; 62(3):864-74. PMC: 3581196. DOI: 10.2337/db12-1089. View

13.

Vijayakumar A, Wu Y, Sun H, Li X, Jeddy Z, Liu C . Targeted loss of GHR signaling in mouse skeletal muscle protects against high-fat diet-induced metabolic deterioration. Diabetes. 2011; 61(1):94-103. PMC: 3237669. DOI: 10.2337/db11-0814. View

14.

Furigo I, de Souza G, Teixeira P, Guadagnini D, Frazao R, List E . Growth hormone enhances the recovery of hypoglycemia ventromedial hypothalamic neurons. FASEB J. 2019; 33(11):11909-11924. PMC: 6902665. DOI: 10.1096/fj.201901315R. View

15.

Young J, Henry B, Benencia F, Bell S, List E, Kopchick J . GHR Mice are protected from obesity-related white adipose tissue inflammation. J Neuroendocrinol. 2020; 32(11):e12854. PMC: 7554100. DOI: 10.1111/jne.12854. View

16.

Mace A, Hamrouni K, Gauthier E, Jean M, Vanthuyne N, Frederic L . Circularly Polarized Fluorescent Helicene-Boranils: Synthesis, Photophysical and Chiroptical Properties. Chemistry. 2021; 27(29):7959-7967. DOI: 10.1002/chem.202100356. View

17.

Quaresma P, Teixeira P, Furigo I, Wasinski F, Couto G, Frazao R . Growth hormone/STAT5 signaling in proopiomelanocortin neurons regulates glucoprivic hyperphagia. Mol Cell Endocrinol. 2019; 498:110574. PMC: 6814575. DOI: 10.1016/j.mce.2019.110574. View

18.

Stout M, Tchkonia T, Pirtskhalava T, Palmer A, List E, Berryman D . Growth hormone action predicts age-related white adipose tissue dysfunction and senescent cell burden in mice. Aging (Albany NY). 2014; 6(7):575-86. PMC: 4153624. DOI: 10.18632/aging.100681. View

19.

Li X, Bartke A, Berryman D, Funk K, Kopchick J, List E . Direct and indirect effects of growth hormone receptor ablation on liver expression of xenobiotic metabolizing genes. Am J Physiol Endocrinol Metab. 2013; 305(8):E942-50. PMC: 3798695. DOI: 10.1152/ajpendo.00304.2013. View

20.

Westbrook R, Bonkowski M, Strader A, Bartke A . Alterations in oxygen consumption, respiratory quotient, and heat production in long-lived GHRKO and Ames dwarf mice, and short-lived bGH transgenic mice. J Gerontol A Biol Sci Med Sci. 2009; 64(4):443-51. PMC: 2657169. DOI: 10.1093/gerona/gln075. View