PMID- 34114278
OWN - NLM
STAT- MEDLINE
DCOM- 20220331
LR  - 20220401
IS  - 1469-445X (Electronic)
IS  - 0958-0670 (Linking)
VI  - 106
IP  - 8
DP  - 2021 Aug
TI  - Vector-mediated expression of muscle specific kinase restores specific force to 
      muscles in the mdx mouse model of Duchenne muscular dystrophy.
PG  - 1794-1805
LID - 10.1113/EP089439 [doi]
AB  - NEW FINDINGS: What is the central question of this study? The 
      (dystrophin-deficient) muscles of mdx mice generate less contractile force per 
      cross-sectional area (specific force) than those of healthy wild-type mice: what 
      is the influence of muscle specific kinase (MuSK) upon the properties of the 
      tibialis anterior (TA) muscle in mdx mice? What is the main finding and its 
      importance? Injection of adeno-associated viral vector encoding MuSK into the TA 
      muscle of young mdx mice increased the specific force of the muscle, suggesting 
      the MuSK signalling system has the potential to restore healthy growth to 
      dystrophin-deficient muscles. ABSTRACT: In the mdx mouse model of Duchenne 
      muscular dystrophy, muscle fibres are fragile and prone to injury and 
      degeneration. Compared to wild-type mice, muscles of mdx mice also develop less 
      specific force (contractile force/cross-sectional area). We recently reported 
      that injecting adeno-associated viral vector encoding muscle specific kinase 
      (AAV-MuSK) into muscles of mdx mice increased utrophin expression and made the 
      muscles more resistant to acute stretch-induced injury. Here we injected AAV-MuSK 
      unilaterally into the tibialis anterior muscle of mdx mice at a younger age 
      (4 weeks), and recorded contraction force from the muscles in situ at 12 weeks of 
      age. Compared to contralateral empty-vector control muscles, muscles injected 
      with AAV-MuSK produced 28% greater specific force (P = 0.0005). They did not 
      undergo the compensatory hypertrophy that normally occurs in muscles of mdx mice. 
      Injection of AAV encoding rapsyn (a downstream effector of MuSK signalling) 
      caused no such improvement in muscle strength. Muscles injected with AAV-MuSK 
      displayed a 10% reduction in the number of fibres with centralized nuclei 
      (P = 0.0015). Our results in mdx mice suggest that elevating the expression of 
      MuSK can reduce the incidence of muscle fibre regeneration and improve the 
      strength of dystrophin-deficient muscles.
CI  - (c) 2021 The Authors. Experimental Physiology (c) 2021 The Physiological Society.
FAU - Ban, Joanne
AU  - Ban J
AD  - Physiology and Bosch Institute, University of Sydney, Sydney, NSW, Australia.
FAU - Beqaj, Besa
AU  - Beqaj B
AD  - Physiology and Bosch Institute, University of Sydney, Sydney, NSW, Australia.
FAU - Phillips, William D
AU  - Phillips WD
AUID- ORCID: 0000-0002-5405-8422
AD  - Physiology and Bosch Institute, University of Sydney, Sydney, NSW, Australia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210623
PL  - England
TA  - Exp Physiol
JT  - Experimental physiology
JID - 9002940
RN  - 0 (Dystrophin)
SB  - IM
MH  - Animals
MH  - Dystrophin/metabolism
MH  - Mice
MH  - Mice, Inbred mdx
MH  - Muscle Contraction/physiology
MH  - Muscle Strength
MH  - Muscle, Skeletal/physiology
MH  - *Muscular Dystrophy, Duchenne/metabolism
OTO - NOTNLM
OT  - MuSK
OT  - dystrophin
OT  - utrophin
EDAT- 2021/06/12 06:00
MHDA- 2022/04/01 06:00
CRDT- 2021/06/11 07:08
PHST- 2021/02/07 00:00 [received]
PHST- 2021/06/08 00:00 [accepted]
PHST- 2021/06/12 06:00 [pubmed]
PHST- 2022/04/01 06:00 [medline]
PHST- 2021/06/11 07:08 [entrez]
AID - 10.1113/EP089439 [doi]
PST - ppublish
SO  - Exp Physiol. 2021 Aug;106(8):1794-1805. doi: 10.1113/EP089439. Epub 2021 Jun 23.