XXXV Reunião Anual da SBBqResumoID:8867


Distinct Pattern of Glycosaminoglycans and Collagen Content in Skeletal Muscles of Mdx Mice with Duchenne-Type Muscular Dystrophy


1, 2 Pereira, R.S.; 1 Tovar, A.M.F.; 2 Quirico-Santos,T.; 1 Mourão, P.A.S.



1 Laboratory of Connective Tissue, HUCFF, UFRJ, RJ, Brazil.
2 Laboratory of Cellular Pathology, IB, UFF, RJ, Brazil.


Mdx mouse, the experimental model of Duchenne Muscular Dystrophy (DMD), develops a severe X-linked recessive disorder, which results in progressive degeneration of skeletal muscle fibres and connective tissue replacement. We previously reported differences in the pattern of muscular lesion between male and female mdx mice. Mdx males with 6 weeks (wks) present severe injury with prominent myonecrosis and low degree of regeneration. In contrast, mdx females at 48 wks presented intense fibrosis and deposition of adipose tissue. This work aimed to establish whether gender dimorphism may influence the expression of collagen and glycosaminoglycans (GAGs) in the gastrocnemic and diaphragm muscles of dystrophic mice at ages characterized by myonecrosis (6 wks), regeneration (12 wks) and fibrosis (24 and 48 wks). GAGs were extracted by papain digestion and purified by cetylpyridinium chloride / ethanol precipitation. Total GAGs concentration was assessed by  hexuronic acid assay using carbazol method and sulfated GAGs by agarose gel electrophoresis. Collagen content was determinate by quantification of hydroxyproline. Gastrocnemic muscles of mdx male mice showed an increase on the deposition of collagen at 12 and 48 wks (p < 0,01) in comparison to C57 age-matched male mice, whereas similar pattern was observed in mdx females at 6 and 48 wks (p < 0,01). In diaphragm muscles, mdx males and females presented raised levels of collagen at all the ages. The profile of GAGs expression in the gastrocnemic and diaphragm muscles was different between genders and groups. Dermatan sulfate was the main GAG type observed. When compared collagen and GAGs content, gastrocnemic muscles of dystrophic male mice showed higher collagen levels than GAGs at 12, 24 and 48 wks (p < 0,01), whereas dystrophic female mice presented this pattern only at 48 wks (p < 0,01). In diaphragm muscles of mdx males was observed the same profile that gastrocnemic muscles, although the content of collagen has been more prominent. Mdx females showed higher collagen content higher than GAGs at 6, 24 and 48 wks (p < 0,01), but not at 12 wks (p < 0,01). Regardless the gender, mdx mice showed more severe alterations in the diaphragm in comparison to gastrocnemic muscles, despite it has been less prominent in mdx females. Although preliminary, these results suggest a possible feedback in the GAGs and collagen synthesis, which could be influencing tissue pathology at distinct skeletal muscles of mdx mice.




Supported by: CAPES, CNPq and FAPERJ.