PuSH - Publication Server of Helmholtz Zentrum München

Gerwin, L. ; Rossmanith, S.* ; Haupt, C.* ; Schultheiß, J.* ; Brinkmeier, H.* ; Bittner, R.E.* ; Kröger, S.*

Impaired muscle spindle function in murine models of muscular dystrophy.

J. Physiol.-London 598, 1591-1609 (2020)
Publ. Version/Full Text Postprint DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Key points: Muscular dystrophy patients suffer from progressive degeneration of skeletal muscle fibres, sudden spontaneous falls, balance problems, as well as gait and posture abnormalities. Dystrophin- and dysferlin-deficient mice, models for different types of muscular dystrophy with different aetiology and molecular basis, were characterized to investigate if muscle spindle structure and function are impaired. The number and morphology of muscle spindles were unaltered in both dystrophic mouse lines but muscle spindle resting discharge and their responses to stretch were altered. In dystrophin-deficient muscle spindles, the expression of the paralogue utrophin was substantially upregulated, potentially compensating for the dystrophin deficiency. The results suggest that muscle spindles might contribute to the motor problems observed in patients with muscular dystrophy. Abstract: Muscular dystrophies comprise a heterogeneous group of hereditary diseases characterized by progressive degeneration of extrafusal muscle fibres as well as unstable gait and frequent falls. To investigate if muscle spindle function is impaired, we analysed their number, morphology and function in wildtype mice and in murine model systems for two distinct types of muscular dystrophy with very different disease aetiology, i.e. dystrophin- and dysferlin-deficient mice. The total number and the overall structure of muscle spindles in soleus muscles of both dystrophic mouse mutants appeared unchanged. Immunohistochemical analyses of wildtype muscle spindles revealed a concentration of dystrophin and β-dystroglycan in intrafusal fibres outside the region of contact with the sensory neuron. While utrophin was absent from the central part of intrafusal fibres of wildtype mice, it was substantially upregulated in dystrophin-deficient mice. Single-unit extracellular recordings of sensory afferents from muscle spindles of the extensor digitorum longus muscle revealed that muscle spindles from both dystrophic mouse strains have an increased resting discharge and a higher action potential firing rate during sinusoidal vibrations, particularly at low frequencies. The response to ramp-and-hold stretches appeared unaltered compared to the respective wildtype mice. We observed no exacerbated functional changes in dystrophin and dysferlin double mutant mice compared to the single mutant animals. These results show alterations in muscle spindle afferent responses in both dystrophic mouse lines, which might cause an increased muscle tone, and might contribute to the unstable gait and frequent falls observed in patients with muscular dystrophy.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Dysferlin ; Dystrophin ; Muscle Spindle ; Muscular Dystrophy ; Proprioception ; Utrophin; Elevated Free Calcium; Skeletal-muscle; Mdx Mouse; Neuromuscular-junctions; Contractile Properties; Membrane Repair; Dysferlin Gene; Utrophin Gene; Protein; Duchenne
ISSN (print) / ISBN 0022-3751
e-ISSN 1469-7793
Journal Journal of Physiology - London
Quellenangaben Volume: 598, Issue: 8, Pages: 1591-1609 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Noboken, UK
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Stem Cell Research (ISF)