Werdnig-Hoffmann disease: myosin isoform expression not arrested at prenatal stage of development

Sawchak, Judith A.; Benoff, B.; Sher, Joanna; Shafiq, Saiyid A.

doi:10.1016/0022-510x(90)90241-e

Cited by 9 publications

(2 citation statements)

References 20 publications

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“…For fMHC and sMHC expression analysis, a total of 33,181 control myotubes (15,675 Type II SMA myotubes and 26,846 Type I SMA myotubes) were counted. Given the similar results obtained in upper and lower limbs, data from these sections were pooled for each sample.…”

Section: Expression Analysis Of Myotubesmentioning

confidence: 99%

Abnormalities in Early Markers of Muscle Involvement Support a Delay in Myogenesis in Spinal Muscular Atrophy

Martínez-Hernández

Bernal

Alías

et al. 2014

J Neuropathol Exp Neurol

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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.

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Section: Expression Analysis Of Myotubesmentioning

confidence: 99%

Abnormalities in Early Markers of Muscle Involvement Support a Delay in Myogenesis in Spinal Muscular Atrophy

Martínez-Hernández

Bernal

Alías

et al. 2014

J Neuropathol Exp Neurol

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“…Along these lines, it has been maintained that myonuclei in muscles of SMA 1 patients undergo apoptosis (41,138). While Fitzsimmons and Hoh (43) and Biral et al (6) found fetal myosin in muscles from patients with SMA 1, this could not be confirmed by others (120,136). Hence, the matter is still open for discussion.…”

Section: Histopathology and Histogenesismentioning

confidence: 99%

Spinal Muscular Atrophy: Present State

Schmalbruch

Haase

2001

Brain Pathology

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Spinal muscular atrophy (SMA) is a hereditary neurodegenerative disease caused by homozygous deletions or mutations in the SMN1 gene on Chr.5q13. SMA spans from severe Werdnig‐Hoffmann disease (SMA 1) to relatively benign Kugelberg‐Welander disease (SMA 3). Onset before birth possibly aggravates the clinical course, because immature motoneurons do not show compensatory sprouting and collateral reinnervation, and motor units in SMA 1, in contrast to those in SMA 3, are not enlarged. Genetic evidence indicates that SMN2, a gene 99% identical to SMN1, can attenuate SMA severity: in patients, more SMN2 copies and higher SMN protein levels are correlated with milder SMA. There is evidence that SMN plays a role in motoneuron RNA metabolism, but it has also been linked to apoptosis. Several mouse models with motoneuron disease have been successfully treated with neurotrophic factors. None of these models is, however, homologous to SMA. Recently, genetic mouse models of SMA have been created by introducing human SMN2 transgenes into Smn knockout mice or by targeting the Smn gene knockout to neurons. These mice not only provide important insights into the pathogenesis of SMA but are also crucial for testing new therapeutic strategies. These include SMN gene transfer, molecules capable to up‐regulate SMN expression and trophic or antiapoptotic factors.

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Skeletal Muscle and Peripheral Nerves

Barbet¹

2001

Fetal and Neonatal Pathology

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Werdnig-Hoffmann disease: myosin isoform expression not arrested at prenatal stage of development

Cited by 9 publications

References 20 publications

Abnormalities in Early Markers of Muscle Involvement Support a Delay in Myogenesis in Spinal Muscular Atrophy

Abnormalities in Early Markers of Muscle Involvement Support a Delay in Myogenesis in Spinal Muscular Atrophy

Spinal Muscular Atrophy: Present State

Skeletal Muscle and Peripheral Nerves

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