title: Muscle spindles exhibit core lesions and extensive degeneration of intrafusal fibers in the Ryr1(I4895T/wt) mouse model of core myopathy.
abstract: Muscle spindles from the hind limb muscles of adult Ryr1(I4895T/wt) (IT/+) mice exhibit severe structural abnormalities. Up to 85% of the spindles are separated from skeletal muscle fascicles by a thick layer of connective tissue. Many intrafusal fibers exhibit degeneration, with Z-line streaming, compaction and collapse of myofibrillar bundles, mitochondrial clumping, nuclear shrinkage and pyknosis. The lesions resemble cores observed in the extrafusal myofibers of this animal model and of core myopathy patients. Spindle abnormalities precede those in extrafusal fibers, indicating that they are a primary pathological feature in this murine Ryr1-related core myopathy. Muscle spindle involvement, if confirmed for human core myopathy patients, would provide an explanation for an array of devastating clinical features characteristic of these diseases and provide novel insights into the pathology of RYR1-related myopathies.
authors.affiliation: Banting and Best Department of Medical Research, University of Toronto, Charles H. Best Institute, 112 College Street, Toronto, ON M5G 1L6, Canada.
authors.forename: Elena
authors.initials: E
authors.lastname: Zvaritch
authors.affiliation: Banting and Best Department of Medical Research, University of Toronto, Charles H. Best Institute, 112 College Street, Toronto, ON M5G 1L6, Canada. Electronic address: david.maclennan@utoronto.ca.
authors.forename: David H
authors.initials: DH
authors.lastname: MacLennan
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology*; D009470:Muscle Spindles / Q000378:metabolism* / Q000473:pathology*; D009135:Muscular Diseases / Q000235:genetics* / Q000473:pathology*; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; C000592747:ryanodine receptor 1, mouse
keywords: Core myopathy; Intrafusal fibers; Mouse model; Muscle spindle; Muscle weakness; Ryanodine receptor type 1