title: Immortalized myogenic cells from congenital muscular dystrophy type1A patients recapitulate aberrant caspase activation in pathogenesis: a new tool for MDC1A research.
abstract: 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-α2. 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-α2-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-α2-deficient mice.
  
  
  CONCLUSIONS
  Immortalized MDC1A myogenic cells provide a new resource for studies of pathogenetic mechanisms and for screening possible therapeutic approaches in laminin-α2-deficiency.
authors: Soonsang
authors: S
authors: Yoon
authors: Guido
authors: G
authors: Stadler
authors: Mary Lou
authors: ML
authors: Beermann
authors: Eric V
authors: EV
authors: Schmidt
authors: James A
authors: JA
authors: Windelborn
authors: Peter
authors: P
authors: Schneiderat
authors: Woodring E
authors: WE
authors: Wright
authors: Departments of Neurology and Physiology & Biophysics, Neuromuscular Biology & Disease Group, Boston University School of Medicine, Boston, MA, USA. millerjb@bu.edu.
authors: Jeffrey Boone
authors: JB
authors: Miller