Myostatin Knockout in Mice Increases Myogenesis and Decreases Adipogenesis

Lin, Ji; Arnold, Heather B.; Della‐Fera, Mary Anne; Azain, M. J.; Hartzell, Diane L.; Baile, Clifton A.

doi:10.1006/bbrc.2002.6500

Cited by 273 publications

(201 citation statements)

References 11 publications

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“…Food intake was also increased in Mstn null mice compared with wild-type mice contrary to other reports (Lin et al, 2002;McPherron and Lee, 2002). Compared with previous research, mice in our study seemed to consume less food overall.…”

Section: Discussioncontrasting

confidence: 94%

The myostatin null mutation and clenbuterol administration elicit additive effects in mice

Dilger

Gabriel

Kutzler

et al. 2010

Animal

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In mice, the myostatin (Mstn) null mutation and treatment with clenbuterol both increase muscle growth and decrease fat mass. Our objective was to determine whether mechanistic overlap exists by administering clenbuterol to Mstn null mice. Male Mstn null and wild-type mice of similar genetic backgrounds received either 0 (control) or 20 p.p.m. clenbuterol in tap water free choice for 14 days. Several traits were measured to estimate muscle and fat growth. The Mstn null mutation resulted in increased body and empty carcass weight, increased muscle weights and decreased fat pad weights. Fat content was reduced and protein content was increased in the empty carcasses of Mstn null mice. Similarly, treatment with clenbuterol resulted in increased body and empty carcass weight, increased muscle weights and reduced fat pad weights. Fat content of empty carcasses and viscera was reduced and protein content of empty carcasses was increased with clenbuterol treatment. A significant interaction of genotype and clenbuterol treatment would indicate an altered responsiveness of Mstn null mice to clenbuterol. However, only the weight of gastrocnemius muscles exhibited a significant (P 5 0.01) interaction of genotype and clenbuterol treatment, indicating that Mstn null mice were less responsive to clenbuterol compared with wild-type mice. Thus, for all other traits, the impact of Mstn null mutation and clenbuterol treatment was completely additive. These data suggest that disruption of Mstn function does not alter the response of mice to b-adrenergic agonists.

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Section: Discussioncontrasting

confidence: 94%

The myostatin null mutation and clenbuterol administration elicit additive effects in mice

Dilger

Gabriel

Kutzler

et al. 2010

Animal

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“…As with aging Mstn K/K mice, liver weights are also smaller in these mice as well as in juvenile (1-3 m.o.) Mstn K/K mice (Lin et al 2002), which is consistent with increased negative feedback on pituitary GH, the primary regulator of liver size (Ohlsson et al 2009). Myostatin's role in the spleen is unknown, although it is minimally expressed in the spleens of zebrafish and mice and is significantly upregulated when the former are stressed (Helterline et al 2007).…”

Section: Aging Mice Young Adultsmentioning

confidence: 65%

The aging myostatin null phenotype: reduced adiposity, cardiac hypertrophy, enhanced cardiac stress response, and sexual dimorphism

Jackson¹,

Luong²,

Vang³

et al. 2012

Journal of Endocrinology

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The natural aging process results in the physiological decline of multiple tissues and organ systems. Changes commonly occur with middle age and include decreased skeletal muscle mass, bone mineral density, cardiac output, and insulin sensitivity, and increased adiposity, all of which can contribute to the onset of sarcopenia, osteoporosis, heart failure, or type 2 diabetes. Recent studies suggest that myostatin may influence many of these systems. We therefore sought to determine whether they are affected by aging, especially in 'middle-aged' Mstn K/K mice (12-20 months old (m.o.)). Although body weights were similar in wild-type (WT) and Mstn K/K mice, lean fat-free mass and skeletal muscles composed of predominantly type I, II, and mixed fibers were significantly heavier in Mstn K/K mice. These differences were accompanied by lower total adiposity, especially in female mice, white and brown fat pad weights, and adipocyte size. Hearts were heavier in Mstn K/K mice across a large age range (3-24 m.o.) and exhibited signs of dilated cardiomyopathy at rest, which include lower strain measurements compared with WT myocardium. However, Mstn K/K mice responded better to isoproterenol stress tests with greater increases in fractional shortening and ejection fraction-differences that were again more apparent in females and which are consistent with physiological cardiac hypertrophy. Spleens and kidneys were also smaller, although histologically normal, in Mstn K/K mice. These data together suggest that attenuating myostatin could potentially prevent or possibly treat pathological conditions that develop with age. Additional studies are nevertheless needed to definitively assess potential risks to cardiac function.

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“…The use of whole tissue samples prevents us from reaching conclusions on which cell type is responsible for the androgenic response observed and should be acknowledged. Nevertheless, Lin et al (26) found that fat pad weight and total lipid content of myostatin-null mice were significantly lowered compared with wild-type mice and suggested that increased muscle development in myostatin knock- In this study, we used six time points to examine trends of gene modulation in mice from both sexes. Significant modulations were observed with microarray data using criteria described in METHODS.…”

Section: Discussionmentioning

confidence: 99%