Document Detail


Myotubularin-deficient myoblasts display increased apoptosis, delayed proliferation, and poor cell engraftment.
MedLine Citation:
PMID:  22841819     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
X-linked myotubular myopathy is a severe congenital myopathy caused by deficiency of the lipid phosphatase, myotubularin. Recent studies of human tissue and animal models have discovered structural and physiological abnormalities in myotubularin-deficient muscle, but the impact of myotubularin deficiency on myogenic stem cells within muscles is unclear. In the present study, we evaluated the viability, proliferative capacity, and in vivo engraftment of myogenic cells obtained from severely symptomatic (Mtm1δ4) myotubularin-deficient mice. Mtm1δ4 muscle contains fewer myogenic cells than wild-type (WT) littermates, and the number of myogenic cells decreases with age. The behavior of Mtm1δ4 myoblasts is also abnormal, because they engraft poorly into C57BL/6/Rag1null/mdx5cv mice and display decreased proliferation and increased apoptosis compared with WT myoblasts. Evaluation of Mtm1δ4 animals at 21 and 42 days of life detected fewer satellite cells in Mtm1δ4 muscle compared with WT littermates, and the decrease in satellite cells correlated with progression of disease. In addition, analysis of WT and Mtm1δ4 regeneration after injury detected similar abnormalities of satellite cell function, with fewer satellite cells, fewer dividing cells, and increased apoptotic cells in Mtm1δ4 muscle. These studies demonstrate specific abnormalities in myogenic cell number and behavior that may relate to the progression of disease in myotubularin deficiency, and may also be used to develop in vitro assays by which novel treatment strategies can be assessed.
Authors:
Michael W Lawlor; Matthew S Alexander; Marissa G Viola; Hui Meng; Romain Joubert; Vandana Gupta; Norio Motohashi; Richard A Manfready; Cynthia P Hsu; Ping Huang; Anna Buj-Bello; Louis M Kunkel; Alan H Beggs; Emanuela Gussoni
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't     Date:  2012-07-27
Journal Detail:
Title:  The American journal of pathology     Volume:  181     ISSN:  1525-2191     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-08-20     Completed Date:  2012-11-08     Revised Date:  2014-05-09    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  961-8     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis*
Cell Count
Cell Proliferation
Cell Survival
Disease Progression
Humans
Mice
Mice, Inbred C57BL
Muscle, Skeletal / injuries,  pathology
Myoblasts / metabolism,  pathology*,  transplantation*
PAX7 Transcription Factor / metabolism
Protein Tyrosine Phosphatases, Non-Receptor / deficiency*,  metabolism
Satellite Cells, Skeletal Muscle / metabolism,  pathology
Grant Support
ID/Acronym/Agency:
K08 AR059750/AR/NIAMS NIH HHS; K08 AR059750/AR/NIAMS NIH HHS; L40 AR057721/AR/NIAMS NIH HHS; P50 NS040828/NS/NINDS NIH HHS; P50 NS040828/NS/NINDS NIH HHS; R01 AR044345/AR/NIAMS NIH HHS; R01 AR044345/AR/NIAMS NIH HHS; R01 NS047727/NS/NINDS NIH HHS; R01NS047727/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/PAX7 Transcription Factor; 0/Pax7 protein, mouse; EC 3.1.3.48/Protein Tyrosine Phosphatases, Non-Receptor; EC 3.1.3.48/myotubularin
Comments/Corrections

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