Title

A mutation in α-tropomyosinslow affects muscle strength, maturation and hypertrophy in a mouse model for nemaline myopathy

Document Type

Journal Article

Publisher

Oxford University Press

Faculty

Computing, Health and Science

School

Biomedical and Sports Science

RAS ID

697

Comments

Originally published as: Corbett, M. A., Robinson, C. S., Dunglison, G. F., Yang, N., Joya, J. E., Stewart, A. W., ... & Hardeman, E. C. (2001). A mutation in α-tropomyosinslow affects muscle strength, maturation and hypertrophy in a mouse model for nemaline myopathy. Human molecular genetics, 10(4), 317-328. Original article available here

Abstract

Nemaline myopathy is a hereditary disease of skeletal muscle defined by a distinct pathology of electron-dense accumulations within the sarcomeric units called rods, muscle weakness and, in most cases, a slow oxidative (type 1) fiber predominance. We generated a transgenic mouse model to study this disorder by expressing an autosomal dominant mutant of α-tropomyosinslow previously identified in a human cohort. Rods were found in all muscles, but to varying extents which did not correlate with the amount of mutant protein present. In addition, a pathological feature not commonly associated with this disorder, cytoplasmic bodies, was found in the mouse and subsequently identified in human samples. Muscle weakness is a major feature of this disease and was examined with respect to fiber composition, degree of rod-containing fibers, fiber mechanics and fiber diameter. Hypertrophy of fast, glycolytic (type 2B) fibers was apparent at 2 months of age. Muscle weakness was apparent in mice at 5–6 months of age, mimicking the late onset observed in humans with this mutation. The late onset did not correlate with observed changes in fiber type and rod pathology. Rather, the onset of muscle weakness correlates with an age-related decrease in fiber diameter and suggests that early onset is prevented by hypertrophy of fast, glycolytic fibers. We suggest that the clinical phenotype is precipitated by a failure of the hypertrophy to persist and therefore compensate for muscle weakness.

DOI

10.1093/hmg/10.4.317

 
COinS
 

Link to publisher version (DOI)

10.1093/hmg/10.4.317