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2005 | 52 | 2 | 453-460
Article title

Ultrastructure of diaphragm from dystrophic α-sarcoglycan-null mice.

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α-Sarcoglycan is a 50 kDa single-pass transmembrane glycoprotein exclusively expressed in striated muscle that, together with β-, γ-, and δ-sarcoglycan, forms a sub-complex at the muscle fibre cell membrane. The sarcoglycans are components of the dystrophin-associated glycoprotein (DAG) complex which forms a mechanical link between the intracellular cytoskeleton and extracellular matrix. The DAG complex function is to protect the muscle membrane from the stress of contractile activity and as a structure for the docking of signalling proteins. Genetic defects of DAG components cause muscular dystrophies. A lack or defects of α-sarcoglycan causes the severe type 2D limb girdle muscular dystrophy. α-Sarcoglycan-null (Sgca-null) mice develop progressive muscular dystrophy similar to the human disorder. This animal model was used in the present work for an ultrastructural study of diaphragm muscle. Diaphragm from Sgca-null mouse presents a clear dystrophic phenotype, with necrosis, regeneration, fibre hypertrophy and splitting, excess of collagen and fatty infiltration. Some abnormalities were also observed, such as centrally located nuclei of abnormal shape, fibres containing inclusion bodies within the contractile structure, and fibres with electron-dense material dispersed over almost the entire cell. Additionally, unusual interstitial cells of uncertain identity were detected within muscle fibres. The abnormal ultrastructure of the diaphragm from Sgca-null mice is discussed.
Physical description
  • Nencki Institute of Experimental Biology, Warszawa, Poland
  • CNR Institute of Neuroscience, Laboratory of Muscle Biology and Physiopathology, Department of Biomedical Sciences, University of Padova, Padova, Italy
  • Nencki Institute of Experimental Biology, Warszawa, Poland
  • CNR Institute of Neuroscience, Laboratory of Muscle Biology and Physiopathology, Department of Biomedical Sciences, University of Padova, Padova, Italy
  • Betto R, Senter L, Ceoldo S, Tarricone E, Biral D, Salviati G (1999) Ecto-ATPase activity of α-sarcoglycan (adhalin). J Biol Chem 274: 7907-7912.
  • Biral D, Jakubiec-Puka A, Ciechomska I, Sandri M, Rossini K, Carraro U, Betto R (2000) Loss of dystrophin and some dystrophin-associated proteins with concomitant signs of apoptosis in rat leg muscle overworked in extension. Acta Neuropathol 100: 618-626.
  • Blake DJ, Weir A, Newey SE, Davies KE (2002) Function and genetics of dystrophin and dystrophin-related proteins in muscle. Physiol Rev 82: 291-329.
  • Burbach JA, Schlenker EH, Johnson JL (1987) Morphometry, histochemistry, and contractility of dystrophic hamster diaphragm. Am J Physiol 253: R275-284.
  • De Angelis MS, Palmucci L, Leone M, Doriguzzi C (1991) Centronuclear myopathy: clinical, morphological and genetic characters. A review of 288 cases. J Neurol Sci 103: 2-9.
  • Duclos F, Straub V, Moore SA, Venzke DP, Hrstka RF, Crosbie RH, Durbeej M, Lebakken CS, Ettinger AJ, van der Meulen J, Holt KH, Lim LE, Sanes JR, Davidson BL, Faulkner JA, Williamson R, Campbell KP (1998) Progressive muscular dystrophy in α-sarcoglycan-deficient mice. J Cell Biol 142: 1461-1471.
  • Durbeej M, Campbell KP (2002) Muscular dystrophies involving the dystrophin-glycoprotein complex: an overview of current mouse models. Curr Opin Genet Dev 12: 349-361.
  • Engel AG (1999) Myofibrillar myopathy. Ann Neurol 46: 681-684.
  • Ervasti JM, Campbell KP (1993) A role for the dystrophin-glycoprotein complex as a transmembrane linker between laminin and actin. J Cell Biol 122: 809-823.
  • Goebel HH (2003) Congenital myopathies at their molecular dawning. Muscle Nerve 27: 527-548.
  • Hack AA, Ly CT, Jiang F, Clendenin CJ, Sigrist KS, Wollmann RL, McNally EM (1998) γ-Sarcoglycan deficiency leads to muscle membrane defects and apoptosis independent of dystrophin. J Cell Biol 142: 1279-1287.
  • Hack AA, Groh ME, McNally EM (2000) Sarcoglycans in muscular dystrophy. Microsc Res Tech 48: 167-180.
  • Henry MD, Campbell KP (1996) Dystroglycan: an extracellular matrix receptor linked to the cytoskeleton. Curr Opin Cell Biol 8: 625-631.
  • Jakubiec-Puka A (1985) Reconstruction of the contractile apparatus of striated muscle. I. Muscle maintained in extension. J Muscle Res Cell Motil 6: 385-401.
  • Liu LA, Engvall E (1999) Sarcoglycan isoforms in skeletal muscle. J Biol Chem 274: 38171-38176.
  • Lynch GS, Rafael JA, Hinkle RT, Cole NM, Chamberlain JS, Faulkner JA (1997) Contractile properties of diaphragm muscle segments from old mdx transgenic mice. Am J Physiol 272: C2063-2068.
  • Pasternak C, Wong S, Elson EL (1995) Mechanical function of dystrophin in muscle cells. J Cell Biol 128: 355-361.
  • Pastoret C, Sebille A (1995) mdx Mice show progressive weakness and muscle deterioration with age. J Neurol Sci 129: 97-105.
  • Petrof BJ, Shrager JB, Stedman HH, Kelly AM, Sweeney HL (1993) Dystrophin protects the sarcolemma from stresses developed during muscle contraction. Proc Natl Acad Sci USA 90: 3710-3714.
  • Roberds SL, Leturcq F, Allamand V, Piccolo F, Jeanpierre M, Anderson RD, Lim LE, Lee JC, Tome FMS, Romero NB, Fardeau M, Beckman JS, Kaplan J-C, Campbell KP (1994) Missense mutations in the adhalin gene linked to autosomal recessive muscular dystrophy. Cell 78: 625-633.
  • Sandona D, Gastaldello S, Martinello T, Betto R (2004) Characterization of the ATP-hydrolyzing activity of α-sarcoglycan. Biochem J 381: 105-112.
  • Sarnat HB (1983) Muscle Pathology and Histochemistry, American Society of Clinical Pathologists Press, Chicago.
  • Straub V, Campbell KP (1997) Muscular dystrophies and the dystrophin-glycoprotein complex. Curr Opin Neurol 10: 168-175.
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