Syngeneic Myoblast Transplantation Improves Muscle Function in a Murine Model of X-Linked Myotubular Myopathy

X-linked myotubular myopathy (XLMTM) is an isogenic muscle disease characterized by progressive wasting of skeletal muscle, weakness, and premature death of affected male offspring. Recently, the XLMTM gene knock-in mouse, Mtm1 p.R69C, was found to have a similar phenotype as the MTM1 gene mutation...

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Bibliographic Details
Published in:Cell transplantation 2015-09, Vol.24 (9), p.1887-1900
Main Authors: Lim, Hyun Ju, Joo, Sunyoung, Oh, Seh-Hoon, Jackson, John D., Eckman, Delrae M., Bledsoe, Tiffaney M., Pierson, Christopher R., Childers, Martin K., Atala, Anthony, Yoo, James J.
Format: Article
Language:English
Subjects:
Action Potentials
Animals
Disease Models, Animal
Female
Gene Knock-In Techniques
Genotype
Immunohistochemistry
Male
Mice
Mice, Inbred C57BL
Muscle, Skeletal - cytology
Muscle, Skeletal - physiology
Myoblasts - cytology
Myoblasts - transplantation
MyoD Protein - metabolism
Myogenic Regulatory Factor 5 - metabolism
Myopathies, Structural, Congenital - therapy
Protein Tyrosine Phosphatases, Non-Receptor - genetics
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Summary:X-linked myotubular myopathy (XLMTM) is an isogenic muscle disease characterized by progressive wasting of skeletal muscle, weakness, and premature death of affected male offspring. Recently, the XLMTM gene knock-in mouse, Mtm1 p.R69C, was found to have a similar phenotype as the MTM1 gene mutation in humans (e.g., central nucleation of small myofibers, attenuated muscle strength, and motor unit potentials). Using this rodent model, we investigated whether syngeneic cell therapy could mitigate muscle weakness. Donor skeletal muscle-derived myoblasts were isolated from C57BL6 wild-type (WT) and Mtm1 p.R69C (KI) mice for transplantation into the gastrocnemius muscle of recipient KI mice. Initial experiments demonstrated that donor skeletal muscle-derived myoblasts from WT and KI mice remained in the gastrocnemius muscle of the recipient KI mouse for up to 4 weeks posttransplantation. KI mice receiving syngeneic skeletal muscle-derived myoblasts displayed an increase in skeletal muscle mass, augmented force generation, and increased nerve-evoked skeletal muscle action potential amplitude. Taken together, these results support our hypothesis that syngeneic cell therapy may potentially be used to ameliorate muscle weakness and delay the progression of XLMTM, as application expands to other muscles.
ISSN:0963-6897
1555-3892
DOI:10.3727/096368914X683494