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Dysferlinopathies are a group of muscular dystrophies with autosomal-recessive inheritance caused by mutations in DYSF gene. Dysferlin is a 237 kDa transmembrane protein responsible for reparation of the sarcolemma. It has calcium-sensitive C2 domains and after dysferlin binding with calcium ions the first one activates vesicles fusion and patch mechanism repair. There are number of knockout animal strains with dysferlin gene mutations. Bla/J mice have the ETn retrotransposon inserted in intron 4 of the DYSF gene of wild-type mice - C57Bl/6. The pathogenesis ascertainment of dysferlinopathies is important not only for revealing of physiological function of dysferlin, but its deficiency influence on reparative regeneration of skeletal muscles. In this paper the description of main pathohistological processes in skeletal muscle that take place in mice with dysferlinopathy after acute myotoxic injury is present. This article reviews quantitative evaluation of main pathomorphological processes in reparative regeneration: alteration (necrotized muscle fibers ratio), proliferation (Ki-67-positive myonuclei ratio), differentiation (mean cros-sectional area, percentage of centrinucleated muscle fibers, myo-genin-positive nuclei ratio, slow/fast muscle fibers ratio). It was identified that dysferlin-deficient mice have increased alteration level with more necrotized muscle fibers (35,1% (29,4%; 42,9%) in Bla/J vs. 25,8% (17,9%; 37,4%) in C57Bl/6 on 2 day after alteration, p<0,05) and decreased proliferation index and myogenic differentiation (3,2% (0,06%; 6,9% of myogenin-positive nuclei in Bla/J vs. 6,3% (1,3%; 15,3%) in C57Bl/6 on 4 day after injection) by contrast to control group.

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About the authors

O. N Chernova

Kazan (Volga region) Federal University


M. O Mavlikeev

Kazan (Volga region) Federal University

A. K Zeynalova

Kazan (Volga region) Federal University

A. P Kiyasov

Kazan (Volga region) Federal University

R. V Deev

Human Stem Cells Institute; Ryazan State Medical University named after academician I.P. Pavlov


  1. Toumi H., Best T. The inflammatory response: friend or enemy for muscle injury? Br. J. Sports Med. 2003; 37(4): 284-6.
  2. Чернова О.Н., Корсаков И.Н., Самчук Д.П. и др. Экспериментальные модели для изучения регенерации поперечнополосатой скелетной мышечной ткани. Гены и Клетки 2015; 4: 127-40
  3. Данилов Р.К., Одинцова И.А. Мышечная система. В: Данилов Р.К., редактор. Руководство по гистологии. 2-е изд. СПб: СпецЛит Россия; 2011, Т.1. с. 425-90
  4. Fernandes T.L., Pedrinelli A., Hernandez A.H. Muscle injury - physiopathology, diagnosis, treatment and clinical presentation. Rev. Bras. Ortop. 2011; 46(3): 247-55.
  5. Asfour H.A., Allouh M.Z., Said R.S. Myogenic regulatory factors: The orchestrators of myogenesis after 30 years of discovery. Exp. Biol. Med. (Maywood) 2018; 243(2): 118-28.
  6. Саркисов Д.С. Регенерация и ее клиническое значение. М.: Медицина; 1979. [Sarkisov D.S. Regeneration and its clinical significance. M.: Medicine; 1979].
  7. Campbell K.P., Han R. Dysferlin and muscle membrane repair. Curr. Opin. Cell Biol. 2007; 19(4): 409-16.
  8. Cooper S.T., McNeil P.L. Membrane Repair: Mechanisms and Pathophysiology. Physiol. Rev. 2015; 95(4): 1205-40.
  9. Huang Y., Laval S.H., van Remoortere A. et al. AHNAK, a novel component of the dysferlin protein complex, redistributes to the cytoplasm with dysferlin during skeletal muscle regeneration. FASEB 2007; 21: 732-42.
  10. Huang Y., de Morree A., van Remoortere A. et al. Calpain 3 is a modulator of the dysferlin protein complex in skeletal muscle. Hum. Mol. Genet. 2008; 17: 1855-66.
  11. Sharma A., Yu C., Leung C. et al. A new role for muscle repair protein Dysferlin in Endothelial Cell Adhesion and Angiogenesis - R2. Arterioscler. Thromb. Vasc. Biol. 2010; 30(11): 2196-204.
  12. Kobayashi K., Izawa T., Kuwamura M. et al. Dysferlin and Animal Models for Dysferlinopathy. J. Toxicol. Pathol. 2012; 25(2): 135-47.
  13. Foster A.H., Carlson B.M. Myotoxicity of local anesthetics and regeneration of the damaged muscle fibers. Anesth. Analg. 1980; 59(10): 727-36.
  14. Генин А.М., Ильин А.Е., Капланский А.С. и др. Биоэтические правила проведения исследований на человеке и животных в авиационной, космической и морской медицине. Авиакосмическая и экологическая медицина 2001; 4: 14-20
  15. de Morree A., Flix B., Bagaric I. et al. Dysferlin Regulates Cell Adhesion in Human Monocytes. J. Biol. Chem. 2013; 288(20): 14147-57.
  16. Chiu Y.H., Hornsey M.A., Klinge L. et al. Attenuated muscle regeneration is a key factor in dysferlin-deficient muscular dystrophy. Hum. Mol. Genet. 2009; 18(11): 1976-89.
  17. Baek J.H., Many G.M., Evesson F.J. et al. Dysferlinopathy Promotes an Intramuscle Expansion of Macrophages with a Cyto-Destructive Phenotype. Am. J. Pathol. 2017; 187(6): 1245-57.
  18. Middel V., Zhou L., Takamiya M. et al. Dysferlin-mediated phospha-tidylserine sorting engages macrophages in sarcolemma repair. Nat. Commun. 2016; 7: 12875.
  19. Schultz E., Lipton B.H. Skeletal muscle satellite cells: Changes in proliferation potential as a function of age. Mech. Ageing Dev. 1983; 20: 377-83.
  20. Roman W., Gomess E.R. Nuclear positioning in skeletal muscle. Semin. Cell Dev. Biol. 2018; 82: 51-6.
  21. Cadot B., Gache V., Vasyutina E. et al. Nuclear movement during myotube formation is microtubule and dynein dependent and is regulated by Cdc42, Par6 and Par3. EMBO Rep. 2012; 13(8): 741-4.
  22. Cohen T.V., Cohen J.E., Partridge T. Myogenesis in dysferlin-deficient myoblasts is inhibited by an intrinsic inflammatory response. Neuromuscul. Disord. 2012; 22(7): 648-58.
  23. Grounds M.D., Terrill J.R., Radley-Crabb H.G. et al. Lipid accumulation in dysferlin-deficient muscles. Am. J. Pathol. 2014; 184(6): 1668-76.
  24. Santo-Domingo J., Demaurex N. Calcium uptake mechanisms of mitochondria. Biochim. Biophys. Acta 2010; 1797(6): 907-12.

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