title: Exercise-induced alterations and loss of sarcomeric M-line organization in the diaphragm muscle of obscurin knockout mice.
abstract: We recently reported that skeletal muscle fibers of obscurin knockout (KO) mice present altered distribution of ankyrin B (ankB), disorganization of the subsarcolemmal microtubules, and reduced localization of dystrophin at costameres. In addition, these mice have impaired running endurance and increased exercise-induced sarcolemmal damage compared with wild-type animals. Here, we report results from a combined approach of physiological, morphological, and structural studies in which we further characterize the skeletal muscles of obscurin KO mice. A detailed examination of exercise performance, using different running protocols, revealed that the reduced endurance of obscurin KO animals on the treadmill depends on exercise intensity and age. Indeed, a mild running protocol did not evidence significant differences between control and obscurin KO mice, whereas comparison of running abilities of 2-, 6-, and 11-mo-old mice exercised at exhaustion revealed a progressive age-dependent reduction of the exercise tolerance in KO mice. Histological analysis indicated that heavy exercise induced leukocyte infiltration, fibrotic connective tissue deposition, and hypercontractures in the diaphragm of KO mice. On the same line, electron microscopy revealed that, in the diaphragm of exercised obscurin KO mice, but not in the hindlimb muscles, both M-line and H-zone of sarcomeres appeared wavy and less defined. Altogether, these results suggest that obscurin is required for the maintenance of morphological and ultrastructural integrity of skeletal muscle fibers against damage induced by intense mechanical stress and point to the diaphragm as the skeletal muscle most severely affected in obscurin-deficient mice.
authors: Molecular Medicine Section, Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors: D
authors: D
authors: Randazzo
authors: Venetian Institute of Molecular Medicine, Padua, Italy.|Interuniversity Institute of Myology.
authors: B
authors: B
authors: Blaauw
authors: Center for Research on Ageing and Translational Medicine & Department of Neuroscience, Imaging, and Clinical Sciences, University G. d'Annunzio of Chieti, Chieti, Italy.|Interuniversity Institute of Myology.
authors: C
authors: C
authors: Paolini
authors: Molecular Medicine Section, Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors: E
authors: E
authors: Pierantozzi
authors: Molecular Medicine Section, Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors: S
authors: S
authors: Spinozzi
authors: University of California, San Diego School of Medicine, San Diego, California.
authors: S
authors: S
authors: Lange
authors: University of California, San Diego School of Medicine, San Diego, California.
authors: J
authors: J
authors: Chen
authors: Center for Research on Ageing and Translational Medicine & Department of Neuroscience, Imaging, and Clinical Sciences, University G. d'Annunzio of Chieti, Chieti, Italy.|Interuniversity Institute of Myology.
authors: F
authors: F
authors: Protasi
authors: Department of Biomedical Sciences, University of Padua, Padua, Italy; and.|Interuniversity Institute of Myology.
authors: C
authors: C
authors: Reggiani
authors: Molecular Medicine Section, Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy; vincenzo.sorrentino@unisi.it.|Interuniversity Institute of Myology.
authors: V
authors: V
authors: Sorrentino
mesh_terms: D000375:Aging / Q000378:metabolism / Q000473:pathology; D000818:Animals; D017487:Ankyrins / Q000378:metabolism; D003964:Diaphragm / Q000502:physiology* / Q000648:ultrastructure*; D017079:Exercise Tolerance / Q000502:physiology; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000502:physiology; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D010805:Physical Conditioning, Animal / Q000379:methods*; D017346:Protein Serine-Threonine Kinases; D064067:Rho Guanine Nucleotide Exchange Factors; D012518:Sarcomeres / Q000502:physiology* / Q000648:ultrastructure*
chemical_list: D017487:Ankyrins; D020662:Guanine Nucleotide Exchange Factors; D009124:Muscle Proteins; D064067:Rho Guanine Nucleotide Exchange Factors; D017346:Protein Serine-Threonine Kinases; C515766:obscn protein, mouse
keywords: contraction; fibrosis; muscular dystrophy; myofibrils; myopathy