The role of growth hormone in lines of mice divergently selected on body weight

Hastings, Ian M.; Bootland, Lorna H.; Hill, William G.

doi:10.1017/s0016672300031207

Cited by 16 publications

(16 citation statements)

References 34 publications

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“…These data together suggest that fast-growing strains may already have up-regulated GH and/or its downstream pathways such that further stimulation with this hormone is dampened relative to unselected strains. In mice, although effects of GH protein treatment were found to be similar in fast-growing and slowgrowing strains (39), GH transgenesis had a greater effect in slow-growing strains (40,41). Collectively, these phenotypic data suggest that domestication in vertebrates may be using the same genetic and physiological pathways regulated by the GH endocrine axis.…”

Section: Discussionmentioning

confidence: 84%

Domestication and growth hormone transgenesis cause similar changes in gene expression in coho salmon ( Oncorhynchus kisutch )

Devlin

Sakhrani²,

Tymchuk³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

121

105

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Domestication has been extensively used in agricultural animals to modify phenotypes such as growth rate. More recently, transgenesis of growth factor genes [primarily growth hormone (GH)] has also been explored as a rapid approach to accelerating performance of agricultural species. Growth rates of many fishes respond dramatically to GH gene transgenesis, whereas genetic engineering of domestic mammalian livestock has resulted in relatively modest gains. The most dramatic effects of GH transgenesis in fish have been seen in relatively wild strains that have undergone little or no selection for enhanced growth, whereas genetic modification of livestock necessarily has been performed in highly domesticated strains that already possess very rapid growth. Such fast-growing domesticates may be refractory to further stimulation if the same regulatory pathways are being exploited by both genetic approaches. By directly comparing gene expression in wild-type, domestic, and GH transgenic strains of coho salmon, we have found that domestication and GH transgenesis are modifying similar genetic pathways. Genes in many different physiological pathways show modified expression in domestic and GH transgenic strains relative to wild-type, but effects are strongly correlated. Genes specifically involved in growth regulation (IGF1, GHR, IGF-II, THR) are also concordantly regulated in domestic and transgenic fish, and both strains show elevated levels of circulating IGF1. Muscle expression of GH in nontransgenic strains was found to be elevated in domesticated fish relative to wild type, providing a possible mechanism for growth enhancement. These data have implications for genetic improvement of existing domesticated species and risk assessment and regulation of emerging transgenic strains.

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Section: Discussionmentioning

confidence: 84%

Domestication and growth hormone transgenesis cause similar changes in gene expression in coho salmon ( Oncorhynchus kisutch )

Devlin

Sakhrani²,

Tymchuk³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

121

105

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“…In particular, elevated GH transcription rates might account for the accelerated growth with high protein accretion in the selected lines. 26 For transgenic mice overexpressing GH, it has been demonstrated that accelerated growth is not induced until the age of three weeks. 27 Increased GH levels being the main modulator of IGF-1 transcription 28 is probably the reason for the observed elevation of the IGF-1 serum concentrations in both selected lines, compared to the control group, at the age of three weeks.…”

Section: Discussionmentioning

confidence: 99%

Fat storage capacity in growth-selected and control mouse lines is associated with line-specific gene expression and plasma hormone levels

Timtchenko

Kratzsch

Sauerwein³

et al. 1999

Int J Obes

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OBJECTIVE: For a detailed understanding of the complex traits growth and fat storage, a dissection into single genetic entities is mandatory. Therefore, blood plasma concentrations of hormones and the expression of selected genes were measured in extremely differentiated mouse lines. Genes were selected as candidates which might in¯uence the complex traits body weight and fat accumulation, and which are located in chromosomal regions recently identi®ed to affect trait differences between the lines. SUBJECTS AND MEASUREMENTS: The mouse lines were selected for high body weight (DU6), high carcass protein content (DU6P) and unselected controls (DUKs). In the selected lines DU6 and DU6P, mean body weights at the age of six weeks were about twice as high as the DUKs, whereas total fat weight was increased 2.2-fold in DU6 mice compared to DU6P and 3.2-fold in comparison to DUKs. Blood plasma concentrations of insulin-like growth factor 1 (IGF-1), growth hormone (GH), insulin and leptin, were measured in all lines at three weeks and at six weeks of age. Expression patterns of the genes encoding growth hormone (Gh), insulin-like growth factor 1 (Igf1), lipoprotein lipase (Lpl), glycerolphosphate dehydrogenase 1 (GDC-1), and adipocyte protein 2 (Ap2) were analyzed by Northern blot hybridization. RESULTS: In line DU6, highly signi®cant increased concentrations of insulin and leptin were observed at six weeks of age; at this stage, IGF-1 concentrations were elevated in the two selected lines compared to controls with maximal concentrations of IGF-1 and GH in DU6P. The amount of mRNA for GH in the pituitary gland, for Igf1 in the liver and for LPL in epididymal fat tissue was signi®cantly elevated in the two selected lines compared to controls at the age of three weeks, but not at six weeks. IGF-1 and GDC-1 mRNA concentrations were signi®cantly higher in the DU6 mice than in the DU6P (P`0.01) and the DUKs (P`0.001) mice examined at both ages. CONCLUSIONS: The results prove line-speci®c concentrations of the analyzed hormones and the transcription amounts of Gh, Igf1, GDC-1 and Lpl. The measured differences are either direct genetic effects or secondary changes, resulting from different food consumption.

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“…In previous experiments on our body weight lines, growth of lit\lit homozygotes on a high line background was more depressed than growth of the low selected lines in absolute terms, but was of similar proportion (Hastings et al, 1993). In a later study (Bu$ nger et al, 1998 b), significant differences were also found on the log scale, but they were relatively small.…”

Section: Introductionmentioning

confidence: 53%

“…In a later study (Bu$ nger et al, 1998 b), significant differences were also found on the log scale, but they were relatively small. Further, exogenous GH administration to wild-type and to lit\lit mice gave similar proportionate responses in weight gain in the high and low lines but much larger absolute responses in the lit\lit animals (Hastings et al, 1993). A significant effect of the lit gene on fatness and a higher increase of fatness in the high than in the low body weight line were found.…”

Section: Introductionmentioning

confidence: 73%

“…At the age of selection, 70 d(ays), the high body weight line is 3 times as heavy as the low body weight line, but these lines differ little in proportion of fat (Hastings et al, 1993 ;. The fat line has 5-to 6-fold higher fat percentage of body weight than the lean line at 98 d, this ratio increasing with age, but the lines differ little in fat-free body weight (Hastings et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

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Role of growth hormone in the genetic change of mice divergently selected for body weight and fatness

Bünger

Hill

1999

Genet. Res.

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To elucidate the involvement of growth hormone (GH) in the genetic change produced by long-term selection in growth and fatness, a 'GH knock-out study' on over 900 mice was undertaken. Lines used had been selected for more than 50 generations for high (PH) and low (PL) body weight (initially protein mass) at 70 d(ays) and for high (F) and low fat content (L) at 98 d, producing a 3-fold difference in body weight and a 5-fold difference in fat content. GH deficiency was achieved by repeated backcrossing into each line a recessive mutant gene (lit) which has a defective GH releasing factor receptor. In the absence of GH, the P lines still differ in body weight (21 d to 98 d): e.g. at 98 d homozygous lit/lit: PH = 24.2 g, PL = 10.0 g; wild-type (wt): PH = 57.4 g, PL = 18.7 g. The effect of the GH deficiency on body weight (untransformed) was very much larger in the PH than in the PL line, but the interaction was much smaller, although still significant, on the log scale. This indicates that changes in the GH system contribute only a small part of the selection response in growth. GH deficiency increased fat percentage in all lines (including P), especially in males (99 d, males lit/lit: F = 26.4%, L = 6.9%; wt: F = 22.0%, L = 4.8%; females: 20.2%, 5.2%, 20.7%, 3.0%) with significant genotype x line and genotype x sex interactions. The interactions between the effects of the lit gene and the genetic background were, however, relatively small compared with these main effects and again indicate that other systems contributed most of the selection response.

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The role of growth hormone in lines of mice divergently selected on body weight

Cited by 16 publications

References 34 publications

Domestication and growth hormone transgenesis cause similar changes in gene expression in coho salmon ( Oncorhynchus kisutch )

Domestication and growth hormone transgenesis cause similar changes in gene expression in coho salmon ( Oncorhynchus kisutch )

Fat storage capacity in growth-selected and control mouse lines is associated with line-specific gene expression and plasma hormone levels

Role of growth hormone in the genetic change of mice divergently selected for body weight and fatness

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