Abstract
Dysferlin is a sarcolemmal muscle protein associated with the processes of membrane repair, trafficking, and fusion of intracellular vesicles and muscle regeneration. Mutations in the DYSF gene cause clinically distinct forms of muscular dystrophies. The dysferlin-deficient SJL/J mouse model presents a reduction of 85% of the protein but shows mild weakness and discrete histopathological alterations. To study the effect of dysferlin deficiency in the muscle regenerative process, we used a model of electrical injury by electroporation to induce muscle degeneration/regeneration in the SJL/J mouse. The relative expression of the genes Pax7, MyoD, Myf5, and Myog was accompanied by the histopathological evaluation during muscle recovery at different time points after injury. We also investigated the effects of dysferlin deficiency in the expression of genes encoding FAM65B and HDAC6 proteins, recently described as forming a tricomplex with dysferlin at the beginning of myoblast differentiation. We observed an altered time course through the process of degeneration and regeneration in dysferlin-deficient mice, with remarkable regenerative capacity characterized by a faster and effective response in the first days after injury, as compared to the WT mice. Also, dysferlin deficiency seems to significantly alter the gene expression of Fam65b and Hdac6 during regeneration, since higher levels of expression of both genes were observed in dysferlin-deficient mice. These results need further attention to define their relevance in the disease mechanism.
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Acknowledgements
The authors would like to thank the scientific and technical support of the team of the Human Genome Research Center.
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This work was supported by Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (CNPq projetos 404664/2012-1 e 456522/2014-0), Fundação de Amparo à Pesquisa do Estado de São Paulo—Centro de Pesquisa, Inovação e Difusão (FAPESP-CEPID- projeto 2013/08028-1), CNPq-INCT (Projeto no: 610031/2009-0), Financiadora de Estudos e Projetos (FINEP—projeto 01.08.0579.00) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).
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Ishiba, R., Santos, A.L.F., Almeida, C.F. et al. Faster regeneration associated to high expression of Fam65b and Hdac6 in dysferlin-deficient mouse. J Mol Hist 50, 375–387 (2019). https://doi.org/10.1007/s10735-019-09834-y
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DOI: https://doi.org/10.1007/s10735-019-09834-y