Endocrine parameters and phenotypes of the growth hormone receptor gene disrupted (GHR-/-) mouse - PubMed (original) (raw)

Review

Endocrine parameters and phenotypes of the growth hormone receptor gene disrupted (GHR-/-) mouse

Edward O List et al. Endocr Rev. 2011 Jun.

Abstract

Disruption of the GH receptor (GHR) gene eliminates GH-induced intracellular signaling and, thus, its biological actions. Therefore, the GHR gene disrupted mouse (GHR-/-) has been and is a valuable tool for helping to define various parameters of GH physiology. Since its creation in 1995, this mouse strain has been used by our laboratory and others for numerous studies ranging from growth to aging. Some of the most notable discoveries are their extreme insulin sensitivity in the presence of obesity. Also, the animals have an extended lifespan, which has generated a large number of investigations into the roles of GH and IGF-I in the aging process. This review summarizes the many results derived from the GHR-/- mice. We have attempted to present the findings in the context of current knowledge regarding GH action and, where applicable, to discuss how these mice compare to GH insensitivity syndrome in humans.

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Figures

Fig. 1.

Size comparison of the three genotypes of the GHR−/− mice; WT (left), heterozygous (center), and homozygous (right) GHR−/− mice.

Fig. 2.

Absolute fat mass and lean mass for male (top) and female (bottom) GHR−/− mice (right) and WT controls (left). Data are expressed as mean ±

sem

; n = 7 male GHR−/−, 6 male WT, 8 female GHR−/−, and 8 female WT mice. Using the same cohort of mice, weight and body composition measurements were taken periodically up to 112 wk of age in duplicate using the Bruker Minispec. [Reproduced with permission from D. E. Berryman et al., Two-year body composition analyses of long-lived GHR null mice. J Gerontol A Biol Sci Med Sci 65:31–40, 2010 (32).]

Fig. 3.

Regional body fat distribution of male control mice (top) and male GHR−/− mice (bottom) using magnetic resonance images. The serial images are acquired using a Bruker 4T small animal magnetic resonance scanner and a T1-weighted multi-echo spin echo acquisition (matrix, 128 × 512 × 128; field of view, 2.5 cm × 10 cm × 2.5 cm; resolution, 0.1953 × 0.1953 × 0.1953 mm3; T1-weighted, 15 echoes; exposure time, 15, 30, 4…225 msec). The mouse is positioned such that the anterior part of the mouse is at the bottom of the image. Image voxels were classified using a multichannel classification algorithm into three classes: 1) fat, 2) lean muscle, and 3) bone/air (156). An interactive segmentation method is used to identify the peritoneum and to label the fat into two groups (intraabdominal and sc). Subcutaneous fat is noted by the color yellow and intraabdominal by the color blue. Male mice were 5 months of age. Images were provided by Kevin Behar and Xenios Papedemtrius at the Yale Mouse Metabolic Phenotyping Center.

Fig. 4.

Right femora images of GHR−/− and WT mice. Right femora of 2-yr-old female (A and B) and male (C and D) GHR−/− (A and C) and WT (B and D) were mounted in foam and scanned using GE eXplore Locus Small Animal MicroCT Scanner at 20 μm voxel, 80 kV, 450 μA, and 2000 msec exposure time. Femora were significantly longer in females. BMD was significantly lower both in male and female GHR−/− compared with WT; however, there were no gender differences (32). [Reproduced with permission from D. E. Berryman et al., Two-year body composition analyses of long-lived GHR null mice. J Gerontol A Biol Sci Med Sci 65:31–40, 2010 (32).]

Fig. 5.

Comparison of life span in male (left) and female (right) WT mice fed ad libitum (AL), WT mice with CR, GHR−/− mice fed AL, and GHR−/− mice with CR. [This figure was modified from M. S. Bonkowski et al., Targeted disruption of growth hormone receptor interferes with the beneficial actions of calorie restriction. Proc Natl Acad Sci USA 103:7901–7905, 2006 (55), with permission. Copyright 2009 National Academy of Sciences.]

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Endocrine parameters and phenotypes of the growth hormone receptor gene disrupted (GHR-/-) mouse - PubMed (original) (raw)