UMass Chan Medical School Faculty Publications

UMMS Affiliation

Wellstone Center for FSHD; Department of Cell and Developmental Biology

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Cell Biology | Cellular and Molecular Physiology | Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Molecular Genetics | Musculoskeletal Diseases


BACKGROUND: Congenital muscular dystrophy Type 1A (MDC1A) is a severe, recessive disease of childhood onset that is caused by mutations in the LAMA2 gene encoding laminin-alpha2. Studies with both mouse models and primary cultures of human MDC1A myogenic cells suggest that aberrant activation of cell death is a significant contributor to pathogenesis in laminin-alpha2-deficiency.

METHODS: To overcome the limited population doublings of primary cultures, we generated immortalized, clonal lines of human MDC1A myogenic cells via overexpression of both CDK4 and the telomerase catalytic component (human telomerase reverse transcriptase (hTERT)).

RESULTS: The immortalized MDC1A myogenic cells proliferated indefinitely when cultured at low density in high serum growth medium, but retained the capacity to form multinucleate myotubes and express muscle-specific proteins when switched to low serum medium. When cultured in the absence of laminin, myotubes formed from immortalized MDC1A myoblasts, but not those formed from immortalized healthy or disease control human myoblasts, showed significantly increased activation of caspase-3. This pattern of aberrant caspase-3 activation in the immortalized cultures was similar to that found previously in primary MDC1A cultures and laminin-alpha2-deficient mice.

CONCLUSIONS: Immortalized MDC1A myogenic cells provide a new resource for studies of pathogenetic mechanisms and for screening possible therapeutic approaches in laminin-alpha2-deficiency.


Caspase-3 activation, Congenital muscular dystrophy, Immortalization of myogenic cells, Laminin-α2-deficiency, Myotube, Telomerase

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Copyright 2013 Yoon et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

DOI of Published Version



Yoon S, Stadler G, Beermann ML, Schmidt EV, Windelborn JA, Schneiderat P, Wright WE, Miller JB. Immortalized myogenic cells from congenital muscular dystrophy type1A patients recapitulate aberrant caspase activation in pathogenesis: a new tool for MDC1A research. Skelet Muscle. 2013 Dec 6;3(1):28. doi: 10.1186/2044-5040-3-28. Link to article on publisher's site

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Link to Article in PubMed

Journal/Book/Conference Title

Skeletal muscle

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