Muscle weakness in respiratory and peripheral skeletal muscles in a mouse model for nebulin-based nemaline myopathy

Barbara Joureau, Josine M. de Winter, Kelly Stam, Henk Granzier, Coen A C Ottenheijm

Research output: Research - peer-reviewArticle

  • 1 Citations

Abstract

Nemaline myopathy is among the most common non-dystrophic congenital myopathies, and is characterized by the presence of nemaline rods in skeletal muscles fibers, general muscle weakness, and hypotonia. Although respiratory failure is the main cause of death in nemaline myopathy, only little is known regarding the contractile strength of the diaphragm, the main muscle of inspiration. To investigate diaphragm contractility, in the present study we took advantage of a mouse model for nebulin-based nemaline myopathy that we recently developed. In this mouse model, exon 55 of Neb is deleted (NebΔExon55), a mutation frequently found in patients. Diaphragm contractility was determined in permeabilized muscle fibers and was compared to the contractility of permeabilized fibers from three peripheral skeletal muscles: soleus, extensor digitorum longus, and gastrocnemius. The force generating capacity of diaphragm muscle fibers of NebΔExon55 mice was reduced to 25% of wildtype levels, indicating severe contractile weakness. The contractile weakness of diaphragm fibers was more pronounced than that observed in soleus muscle, but not more pronounced than that observed in extensor digitorum longus and gastrocnemius muscles. The reduced muscle contractility was at least partly caused by changes in cross-bridge cycling kinetics which reduced the number of bound cross-bridges. The severe diaphragm weakness likely contributes to the development of respiratory failure in NebΔExon55 mice and might explain their early, postnatal death.

LanguageEnglish (US)
Pages83-89
Number of pages7
JournalNeuromuscular Disorders
Volume27
Issue number1
DOIs
StatePublished - Jan 1 2017

Fingerprint

Nemaline Myopathies
Muscle Weakness
Diaphragm
Skeletal Muscle
nebulin
Muscles
Respiratory Insufficiency
Myotonia Congenita
Muscle Hypotonia
Skeletal Muscle Fibers
Cause of Death
Exons
Mutation

Keywords

  • Diaphragm
  • Nebulin
  • Nemaline myopathy
  • Respiratory failure

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Neurology
  • Clinical Neurology
  • Genetics(clinical)

Cite this

Muscle weakness in respiratory and peripheral skeletal muscles in a mouse model for nebulin-based nemaline myopathy. / Joureau, Barbara; de Winter, Josine M.; Stam, Kelly; Granzier, Henk; Ottenheijm, Coen A C.

In: Neuromuscular Disorders, Vol. 27, No. 1, 01.01.2017, p. 83-89.

Research output: Research - peer-reviewArticle

Joureau, Barbara ; de Winter, Josine M. ; Stam, Kelly ; Granzier, Henk ; Ottenheijm, Coen A C. / Muscle weakness in respiratory and peripheral skeletal muscles in a mouse model for nebulin-based nemaline myopathy. In: Neuromuscular Disorders. 2017 ; Vol. 27, No. 1. pp. 83-89
@article{10f7516f72504992a3241455e43262a2,
title = "Muscle weakness in respiratory and peripheral skeletal muscles in a mouse model for nebulin-based nemaline myopathy",
abstract = "Nemaline myopathy is among the most common non-dystrophic congenital myopathies, and is characterized by the presence of nemaline rods in skeletal muscles fibers, general muscle weakness, and hypotonia. Although respiratory failure is the main cause of death in nemaline myopathy, only little is known regarding the contractile strength of the diaphragm, the main muscle of inspiration. To investigate diaphragm contractility, in the present study we took advantage of a mouse model for nebulin-based nemaline myopathy that we recently developed. In this mouse model, exon 55 of Neb is deleted (NebΔExon55), a mutation frequently found in patients. Diaphragm contractility was determined in permeabilized muscle fibers and was compared to the contractility of permeabilized fibers from three peripheral skeletal muscles: soleus, extensor digitorum longus, and gastrocnemius. The force generating capacity of diaphragm muscle fibers of NebΔExon55 mice was reduced to 25% of wildtype levels, indicating severe contractile weakness. The contractile weakness of diaphragm fibers was more pronounced than that observed in soleus muscle, but not more pronounced than that observed in extensor digitorum longus and gastrocnemius muscles. The reduced muscle contractility was at least partly caused by changes in cross-bridge cycling kinetics which reduced the number of bound cross-bridges. The severe diaphragm weakness likely contributes to the development of respiratory failure in NebΔExon55 mice and might explain their early, postnatal death.",
keywords = "Diaphragm, Nebulin, Nemaline myopathy, Respiratory failure",
author = "Barbara Joureau and {de Winter}, {Josine M.} and Kelly Stam and Henk Granzier and Ottenheijm, {Coen A C}",
year = "2017",
month = "1",
doi = "10.1016/j.nmd.2016.10.004",
volume = "27",
pages = "83--89",
journal = "Neuromuscular Disorders",
issn = "0960-8966",
publisher = "Elsevier Limited",
number = "1",

}

TY - JOUR

T1 - Muscle weakness in respiratory and peripheral skeletal muscles in a mouse model for nebulin-based nemaline myopathy

AU - Joureau,Barbara

AU - de Winter,Josine M.

AU - Stam,Kelly

AU - Granzier,Henk

AU - Ottenheijm,Coen A C

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Nemaline myopathy is among the most common non-dystrophic congenital myopathies, and is characterized by the presence of nemaline rods in skeletal muscles fibers, general muscle weakness, and hypotonia. Although respiratory failure is the main cause of death in nemaline myopathy, only little is known regarding the contractile strength of the diaphragm, the main muscle of inspiration. To investigate diaphragm contractility, in the present study we took advantage of a mouse model for nebulin-based nemaline myopathy that we recently developed. In this mouse model, exon 55 of Neb is deleted (NebΔExon55), a mutation frequently found in patients. Diaphragm contractility was determined in permeabilized muscle fibers and was compared to the contractility of permeabilized fibers from three peripheral skeletal muscles: soleus, extensor digitorum longus, and gastrocnemius. The force generating capacity of diaphragm muscle fibers of NebΔExon55 mice was reduced to 25% of wildtype levels, indicating severe contractile weakness. The contractile weakness of diaphragm fibers was more pronounced than that observed in soleus muscle, but not more pronounced than that observed in extensor digitorum longus and gastrocnemius muscles. The reduced muscle contractility was at least partly caused by changes in cross-bridge cycling kinetics which reduced the number of bound cross-bridges. The severe diaphragm weakness likely contributes to the development of respiratory failure in NebΔExon55 mice and might explain their early, postnatal death.

AB - Nemaline myopathy is among the most common non-dystrophic congenital myopathies, and is characterized by the presence of nemaline rods in skeletal muscles fibers, general muscle weakness, and hypotonia. Although respiratory failure is the main cause of death in nemaline myopathy, only little is known regarding the contractile strength of the diaphragm, the main muscle of inspiration. To investigate diaphragm contractility, in the present study we took advantage of a mouse model for nebulin-based nemaline myopathy that we recently developed. In this mouse model, exon 55 of Neb is deleted (NebΔExon55), a mutation frequently found in patients. Diaphragm contractility was determined in permeabilized muscle fibers and was compared to the contractility of permeabilized fibers from three peripheral skeletal muscles: soleus, extensor digitorum longus, and gastrocnemius. The force generating capacity of diaphragm muscle fibers of NebΔExon55 mice was reduced to 25% of wildtype levels, indicating severe contractile weakness. The contractile weakness of diaphragm fibers was more pronounced than that observed in soleus muscle, but not more pronounced than that observed in extensor digitorum longus and gastrocnemius muscles. The reduced muscle contractility was at least partly caused by changes in cross-bridge cycling kinetics which reduced the number of bound cross-bridges. The severe diaphragm weakness likely contributes to the development of respiratory failure in NebΔExon55 mice and might explain their early, postnatal death.

KW - Diaphragm

KW - Nebulin

KW - Nemaline myopathy

KW - Respiratory failure

UR - http://www.scopus.com/inward/record.url?scp=85007273824&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85007273824&partnerID=8YFLogxK

U2 - 10.1016/j.nmd.2016.10.004

DO - 10.1016/j.nmd.2016.10.004

M3 - Article

VL - 27

SP - 83

EP - 89

JO - Neuromuscular Disorders

T2 - Neuromuscular Disorders

JF - Neuromuscular Disorders

SN - 0960-8966

IS - 1

ER -