Elevated insulin-like growth factor 2 expression may contribute to the hypermuscular phenotype of myostatin null mice

Clark, Daniel; Clark, Diana; Hogan, E. K.; Kroscher, Kellie A; Dilger, A. C.

doi:10.1016/j.ghir.2015.06.007

Cited by 12 publications

(15 citation statements)

References 33 publications

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“…A tight correlation between Mstn and Igf2 expression has been previously established (Kalista et al, 2012;Clark et al, 2015). Taken together, although other genes might also participate in this phenotype, we suggest that the upregulation of the growthpromoting Igf2 and Dlk1 genes at the early postnatal P6 stage coupled with the reduced expression of Mstn in the adult muscle are good candidates for the hypertrophic phenotype observed in the H19 Δ3 mutant muscles.…”

Section: Its Reduced Expression In the H19supporting

confidence: 79%

H19 controls reactivation of the imprinted gene network during muscle regeneration

et al. 2016

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The H19 locus controls fetal growth by regulating expression of several genes from the imprinted gene network (IGN). H19 is fully repressed after birth, except in skeletal muscle. Using loss-of-function H19 Δ3 mice, we investigated the function of H19 in adult muscle. Mutant muscles display hypertrophy and hyperplasia, with increased Igf2 and decreased myostatin (Mstn) expression. Many imprinted genes are expressed in muscle stem cells or satellite cells. Unexpectedly, the number of satellite cells was reduced by 50% in H19 Δ3 muscle fibers. This reduction occurred after postnatal day 21, suggesting a link with their entry into quiescence. We investigated the biological function of these mutant satellite cells in vivo using a regeneration assay induced by multiple injections of cardiotoxin. Surprisingly, despite their reduced number, the self-renewal capacity of these cells is fully retained in the absence of H19. In addition, we observed a better regeneration potential of the mutant muscles, with enhanced expression of several IGN genes and genes from the IGF pathway.

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Section: Its Reduced Expression In the H19supporting

confidence: 79%

H19 controls reactivation of the imprinted gene network during muscle regeneration

et al. 2016

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“…These differences from the current study might be attributable to the different muscles selected and ages of mice that were assessed in other studies (2.8 months in our study and 3.2-7 months in the other studies), and may also be explained by differences in the expression of Igf1 and Igf1 receptors, which are crucial for antagonists of TGF-β family members to induce hypertrophy (Kalista et al 2012). In addition, the role of IGF2 in regulating hypertrophy in Mstn −/− mice cannot be overlooked as noted earlier (Clark et al 2015) and may also explain the increase (~40%) in mass of quadriceps muscles in young adult mice when MSTN protein is reduced in skeletal muscles using the Cre/Lox recombinase system to block the expression of Mstn mRNA (Welle et al 2007). We show that the greatly increased concentrations of IGF1 in the transgenic Igf1 + mice enhanced the hypertrophy of skeletal muscle at a younger age, which was particularly evident in Mstn −/− mice.…”

Section: :2mentioning

confidence: 61%

“…The exception was the expression of Igfbp5 mRNA, which was increased in skeletal muscles of Mstn −/− mice. Others have also reported higher expression of Igfbp5 mRNA in skeletal muscles of Mstn −/− mice (Clark et al 2015). While the role of IGFBP5 is unclear, overexpression reduced birth weight and retarded the development of skeletal muscles (Salih et al 2004).…”

Section: :2mentioning

confidence: 96%

“…WT mice (Clark et al 2015). By contrast, concentrations of Igf1 mRNA were reduced in skeletal muscles of Mstn −/− mice up to 3 weeks of age (Clark et al 2015), and the differences between Mstn −/− and WT were further diminished in mice older than 6 weeks (Kocamis et al 2002, Clark et al 2015. The reduced expression of Igf1 mRNA in skeletal muscles of juvenile Mstn −/− mice reported here (Study 1) suggested to us that further growth would occur in skeletal muscles if Igf1 expression was increased during postnatal growth.…”

Section: :2mentioning

confidence: 99%

“…Unlike letters denote significance (P < 0.001). in Mstn −/− mice because concentrations of Igf2 mRNA were higher in muscles of Mstn −/− compared with WT mice postnatally from 3 to 10 weeks of age(Clark et al 2015). While the increased concentrations of Igf2 mRNA prevailed in skeletal muscles of Mstn −/− mice, they progressively decline from birth in both Mstn −/− and…”

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confidence: 97%

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IGF1 stimulates greater muscle hypertrophy in the absence of myostatin in male mice

Hennebry

Oldham

Shavlakadze

et al. 2017

Journal of Endocrinology

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Insulin-like growth factors (IGFs) and myostatin have opposing roles in regulating the growth and size of skeletal muscle, with IGF1 stimulating, and myostatin inhibiting, growth. However, it remains unclear whether these proteins have mutually dependent, or independent, roles. To clarify this issue, we crossed myostatin null () mice with mice overexpressing in skeletal muscle () to generate six genotypes of male mice; wild type ( ), ,, , and Overexpression of increased the mass of mixed fibre type muscles (e.g. ) by 19% over , 33% over and 49% over ( < 0.001). By contrast, the mass of the gonadal fat pad was correspondingly reduced with the removal of and addition of Myostatin regulated the number, while IGF1 regulated the size of myofibres, and the deletion of and independently increased the proportion of fast type IIB myosin heavy chain isoforms in (up to 10% each, < 0.001). The abundance of AKT and rpS6 was increased in muscles of , while phosphorylation of AKT was increased in (, and). Our results demonstrate that a greater than additive effect is observed on the growth of skeletal muscle and in the reduction of body fat when myostatin is absent and IGF1 is in excess. Finally, we show that myostatin and IGF1 regulate skeletal muscle size, myofibre type and gonadal fat through distinct mechanisms that involve increasing the total abundance and phosphorylation status of AKT and rpS6.

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One-step base editing in multiple genes by direct embryo injection for pig trait improvement

Song

Wang

Zheng

et al. 2022

Sci. China Life Sci.

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Elevated insulin-like growth factor 2 expression may contribute to the hypermuscular phenotype of myostatin null mice

Cited by 12 publications

References 33 publications

H19 controls reactivation of the imprinted gene network during muscle regeneration

H19 controls reactivation of the imprinted gene network during muscle regeneration

IGF1 stimulates greater muscle hypertrophy in the absence of myostatin in male mice

One-step base editing in multiple genes by direct embryo injection for pig trait improvement

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