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Gender dimorphism influences extracellular matrix expression and regeneration of muscular tissue in mdx dystrophic mice

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Abstract

Mdx mouse, the animal model of Duchenne muscular dystrophy, lacks dystrophin and develops an X-linked recessive inflammatory myopathy characterized by degeneration of skeletal muscle fibers and connective tissue replacement. The present work aimed to assess whether gender dimorphism in mdx mice would influence skeletal muscle pathology at ages corresponding to main histological changes in the microenvironment of muscular tissue: myonecrosis, regeneration, and fibrosis. At the height of myonecrosis (6 weeks postnatal), skeletal muscles of male mdx mice showed increased sarcolemmal permeability, numerous inflammatory foci, and marked deposition of the extracellular matrix components (ECM) type I collagen and laminin. In contrast, age-matched mdx females showed mild ECM deposition, discrete myonecrosis, but increased numbers of regenerating fibers expressing the satellite cell marker NCAM. In contrast ovariectomized mdx females showed decreased numbers of regenerating fibers. Older (24 and 48 weeks postnatal) mdx females showed extensive fibrosis with increased sarcolemmal permeability and marked deposition of ECM components than corresponding males. These results suggest a role for female hormones in the control of myonecrosis probably by promoting regeneration of muscular tissue and mitigating inflammation especially at ages under the critical influence of sex hormones.

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Acknowledgements

The authors are grateful to Nina M. Cortes and Bartira D. Oliveira for excellent technical assistance and to Dr. Edna Nanami Yamasaki for critical reading of the manuscript. This work received financial support from Program of Neuroimmunology (CAPES) and Faperj.

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Authors and Affiliations

  1. Department of Immunobiology, Institute of Biology, Fluminense Federal University, Rio de Janeiro, Brazil

    Maria Cristina Salimena & Jussara Lagrota-Candido

  2. Department of Cellular and Molecular Biology, Institute of Biology, Fluminense Federal University, Rio de Janeiro, Brazil, 94910-130

    Maria Cristina Salimena & Thereza Quírico-Santos

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  1. Maria Cristina Salimena
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  2. Jussara Lagrota-Candido
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  3. Thereza Quírico-Santos
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Correspondence to Jussara Lagrota-Candido.

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Salimena, M.C., Lagrota-Candido, J. & Quírico-Santos, T. Gender dimorphism influences extracellular matrix expression and regeneration of muscular tissue in mdx dystrophic mice. Histochem Cell Biol 122, 435–444 (2000). https://doi.org/10.1007/s00418-004-0707-8

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