Loss of nNOS inhibits compensatory muscle hypertrophy and exacerbates inflammation and eccentric contraction-induced damage in mdx mice

We studied the effects of sex steroids on muscle weight and oxidative capacity of rat plantaris muscles subjected to functional overload by removal of synergistic muscles. Eight weeks after bilateral synergist removal, plantaris muscles were strikingly hypertrophic compared with unoperated controls. After this period, there were selective alterations in the ability of the muscles to oxidize three substrates of oxidative metabolism. Thus 14CO2 production from [6-14C]glucose and [2-14C]pyruvate was significantly reduced, whereas there was no alteration in 14CO2 production from beta-[3-14C]hydroxybutyrate. Succinate dehydrogenase specific activity was decreased in overloaded muscle. There was no effect of sex hormone status on any of these parameters. Finally, 30 days of functional overload did not influence cytosolic androgen receptor binding. These results are not consistent with the idea that sex steroids and functional overload act synergistically.

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TAT-μUtrophin mitigates the pathophysiology of dystrophin and utrophin double-knockout mice

Journal of Applied Physiology ◽

10.1152/japplphysiol.00248.2011 ◽

2011 ◽

Vol 111 (1) ◽

pp. 200-205 ◽

Cited By ~ 15

Author(s):

Jarrod A. Call ◽

James M. Ervasti ◽

Dawn A. Lowe

Keyword(s):

Knockout Mice ◽

Skeletal Muscles ◽

Ex Vivo ◽

Eccentric Contraction ◽

Mdx Mice ◽

Double Knockout ◽

Replacement Treatment ◽

Generating Capacity

Previously, we demonstrated functional substitution of dystrophin by TAT-μUtrophin (TAT-μUtr) in dystrophin-deficient mdx mice. Herein, we addressed whether TAT-μUtr could improve the phenotype of dystrophin and utrophin double-knockout ( mdx:utr−/−) mice. Specifically, we quantitatively compared survival and quality of life assessments in mdx:utr−/− mice receiving TAT-μUtr protein administration against placebo-treated mdx:utr−/− mice (PBS). Additionally, skeletal muscles from TAT-μUtr and PBS mice were tested in vivo and ex vivo for strength and susceptibility to eccentric contraction-induced injury. We found the TAT-μUtr treatment extended life span 45% compared with mice administered PBS. This was attributed to significantly increased food consumption (3.1 vs. 1.8 g/24 h) due to improved ability to search for food as daily cage activities were greater in TAT-μUtr mice (e.g., 364 vs. 201 m ambulation/24 h). The extensor digitorum longus muscles of TAT-μUtr-treated double-knockout mice also displayed increased force-generating capacity ex vivo (8.3 vs. 6.4 N/cm2) and decreased susceptibility to injury ex vivo and in vivo. These data indicate that the functional benefits of TAT-μUtr replacement treatment extend to the mdx:utr−/− double-knockout mouse and support its development as a therapy to mitigate muscle weakness in patients with Duchenne muscular dystrophy.

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Proteome Dynamics Rapidly Detect Protein Synthetic and Fibrogenic Changes Following Eccentric Contraction‐Induced Muscle Damage in mdx Mice

The FASEB Journal ◽

10.1096/fasebj.29.1_supplement.947.7 ◽

2015 ◽

Vol 29 (S1) ◽

Author(s):

Stephen Stimpson ◽

Fritz Kramer ◽

Todd Shearer ◽

Andrew Billin ◽

Alan Russell ◽

...

Keyword(s):

Muscle Damage ◽

Eccentric Contraction ◽

Mdx Mice

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Myofiber branching rather than myofiber hyperplasia contributes to muscle hypertrophy in mdx mice

Skeletal Muscle ◽

10.1186/2044-5040-4-10 ◽

2014 ◽

Vol 4 (1) ◽

pp. 10 ◽

Cited By ~ 21

Author(s):

Rachel M Faber ◽

John K Hall ◽

Jeffrey S Chamberlain ◽

Glen B Banks

Keyword(s):

Muscle Hypertrophy ◽

Mdx Mice

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The fate of newly formed satellite cells during compensatory muscle hypertrophy

Virchows Archiv B Cell Pathology ◽

10.1007/bf02899148 ◽

1976 ◽

Vol 21 (1) ◽

pp. 113-118

Author(s):

S. Schiaffino ◽

S. Pierobon Bormioli ◽

M. Aloisi

Keyword(s):

Satellite Cells ◽

Muscle Hypertrophy ◽

Compensatory Muscle Hypertrophy

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Desmin is a modifier of dystrophic muscle features in Mdx mice

10.1101/742858 ◽

2019 ◽

Author(s):

Arnaud Ferry ◽

Julien Messéant ◽

Ara Parlakian ◽

Mégane Lemaitre ◽

Pauline Roy ◽

...

Keyword(s):

Neuromuscular Disease ◽

Muscle Hypertrophy ◽

Force Production ◽

Muscle Performance ◽

Mdx Mice ◽

Force Transmission ◽

Dystrophic Muscle ◽

Adeno Associated Virus ◽

Dystrophin Deficiency ◽

Insight Into

AbstractDuchenne muscular dystrophy (DMD) is a severe neuromuscular disease, caused by dystrophin deficiency. Desmin is like dystrophin associated to costameric structures bridging sarcomeres to extracellular matrix that are involved in force transmission and skeletal muscle integrity. In the present study, we wanted to gain further insight into the roles of desmin which expression is increased in the muscle from the mouse Mdx DMD model. We show that a deletion of the desmin gene (Des) in Mdx mice (DKO, Mdx:desmin-/-) induces a marked worsening of the weakness (reduced maximal force production) as compared to Mdx mice. Fragility (higher susceptibility to contraction-induced injury) was also aggravated and fatigue resistance was reduced in DKO mice. Moreover, in contrast to Mdx mice, the DKO mice did not undergo a muscle hypertrophy because of smaller and less numerous fibers, with reduced percentage of centronucleated fibres. Interestingly, Desmin cDNA transfer with adeno-associated virus in 1-month-old DKO mice and newborn Mdx mice improved muscle weakness. Overall, desmin plays important and beneficial roles on muscle performance, fragility and remodelling in dystrophic Mdx mice.

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