Accumulation of collagen and altered fiber‐type ratios as indicators of abnormal muscle gene expression in the mdx dystrophic mouse

Abstract

The growth and development of the X-linked muscular dystrophy mutant mouse (mdx) was compared with a control group from 3 weeks to 1 year old. Quantitative cytological analysis of the soleus muscle revealed cycles of degeneration, regeneration, and hypertrophy, and at any one time it was difficult to assess the extent of the disease based on muscle fiber size. One noticeable difference even in the youngest muscles studied was the reduced numbers of slow oxidative fibers and the increased number of fast glycolytic fibers in the mdx soleus muscles. The collagen of the connective tissue components of selectively stained sections was determined by computerized image analysis. Marked accumulation of collagen was found in both the endomysium and perimysium of the dystrophic muscles as compared with age-matched controls. Since the mdx mouse is a result of the same type of genetic defect as in human Duchenne muscular dystrophy, this model could thus be used to assess the effectiveness of various therapeutic approaches, including gene therapy using muscle fibrosis and fiber type proportions as the indicators.

Diving into old age: muscular senescence in a large-bodied, long-lived mammal, the Weddell seal (Leptonychotes weddellii)

“…As with total collagen content, an adjustment in the ratio of the two key isoforms can influence contractile properties. Exercise training, injury, disease and aging are all associated with some degree of ECM remodeling (Mohan and Radha, 1980;Marshall et al, 1989;Williams et al, 1999;Miller et al, 2001;Mackey et al, 2004). Detectable signs of normal aging in skeletal muscle include increased deposition of total collagen (Mays et al, 1988;Kovanen and Suominen, 1989;Gosselin et al, 1998) resulting from increased resistance to collagen degradation and turnover (Mohan and Radha, 1980), as well as a relatively greater contribution of type I, at the expense of type III, to the collagen pool (Mays et al, 1988;Kovanen and Suominen, 1989).…”

Muscles of mice deficient in α-sarcoglycan maintain large masses and near control force values throughout the life span

“…As observed for limb muscles of mdx mice (5,36,39), single fiber CSAs for EDL or soleus muscles of Sgca-null mice were not greater than those for muscles of WT mice (Table 4). The lack of an increase in average muscle fiber size in Sgca-null mice suggests that any enhanced ability of muscles of Sgcanull mice to generate absolute force is due to an increase in fiber number compared with muscles of WT mice.…”

“…Despite very early onset of pathology in Sgca-null mice (19), Sgca-null mice show an increase in muscle mass relative to WT masses throughout the life span and do not at any age display the muscle wasting that is observed in human LGMD 2D. Both actual myofiber hypertrophy (25,26,33,36) as well as pseudohypertrophy, characterized by proliferation of connective and adipose tissues (16,33,39), have been described in mdx mice and feline and canine models of muscular dystrophy. In the present study, the 50% and 62% larger masses of EDL and soleus muscles, respectively, of 3-mo-old Sgca-null compared with age-matched WT mice are in excellent agreement with the 50% and 70% greater masses of EDL and soleus muscles of Sgca-null mice at 8 wk reported by Duclos et al (19).…”

Molecular Regulation and Rejuvenation of Muscle Stem (Satellite) Cell Aging

“…At the subcellular level, aged muscle ibers display an increased level of mitochondrial abnormalities and susceptibility to apoptosis. (150,151) Myoibers from aged muscle show a reduction in force generation and are more susceptible to contraction-induced injury. (152) In addition to the immediate niche surrounding satellite cells, local interstitial cells, motor neurons, blood vessels, and their associated secretable factors reside within skeletal muscle and have the potential to regulate satellite cell function and affect muscle regeneration.…”