title: Abnormalities in early markers of muscle involvement support a delay in myogenesis in spinal muscular atrophy.
abstract: Spinal muscular atrophy (SMA) is characterized by loss of motor neurons in the spinal cord that results in muscle denervation and profound weakness in affected patients. We sought evidence for primary muscle involvement in the disease during human development by analyzing the expression of several muscle cytoskeletal components (i.e. slow, fast, and developmental myosin, desmin, and vimentin) in fetal or postnatal skeletal muscle samples from 5 SMA cases and 6 controls. At 14 weeks' gestation, SMA samples had higher percentages of myotubes expressing fast myosin and lower percentages of myotubes expressing slow myosin versus control samples. Desmin and vimentin were highly expressed at prenatal stages without notable differences between control and SMA samples, although both proteins showed persistent immunostaining in atrophic fibers in postnatal SMA samples. We also studied the expression of Pax7-positive nuclei as a marker of satellite cells and found no differences between control and SMA prenatal samples. There was, however, a significant increase in satellite cells in postnatal atrophic SMA fibers, suggesting an abnormal myogenic process. Together, these results support the hypothesis of a delay in muscle maturation as one of the primary pathologic components of SMA. Furthermore, myosins and Pax7 may be useful research markers of muscle involvement in this disease.
authors.affiliation: From the Department of Molecular Biology, Hospital La Princesa, Madrid (RM-H); and Department of Genetics, IIB Sant Pau Research Institute, Hospital de Sant Pau and Centro de Investigación Biomédica en Red de Enfermedades Raras (SB, LA); and Department of Clinical and Molecular Genetics, Hospital Valle Hebron, Passeig Valle Hebron (EFT), Barcelona, Spain.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Martínez-Hernández
authors.forename: Sara
authors.initials: S
authors.lastname: Bernal
authors.forename: Laura
authors.initials: L
authors.lastname: Alias
authors.forename: Eduardo F
authors.initials: EF
authors.lastname: Tizzano
mesh_terms: D015415:Biomarkers / Q000032:analysis*; D003893:Desmin / Q000378:metabolism; D003964:Diaphragm / Q000002:abnormalities* / Q000254:growth & development; D005260:Female; D005333:Fetus; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D024510:Muscle Development / Q000235:genetics / Q000502:physiology*; D018482:Muscle, Skeletal / Q000002:abnormalities* / Q000254:growth & development; D009134:Muscular Atrophy, Spinal / Q000235:genetics / Q000473:pathology*; D009218:Myosins / Q000378:metabolism*; D051763:PAX7 Transcription Factor / Q000378:metabolism*; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism / Q000473:pathology; D055540:Survival of Motor Neuron 2 Protein / Q000235:genetics; D014746:Vimentin / Q000378:metabolism
chemical_list: D015415:Biomarkers; D003893:Desmin; D051763:PAX7 Transcription Factor; C497321:PAX7 protein, human; C526477:SMN2 protein, human; D055540:Survival of Motor Neuron 2 Protein; D014746:Vimentin; D009218:Myosins