Identification of a novel mutant transcript of laminin alpha 2 chain gene responsible for muscular dystrophy and dysmyelination in dy2J mice

Hum Mol Genet. 1995 Jun;4(6):1055-61. doi: 10.1093/hmg/4.6.1055.


Murine dystrophia muscularis-2J (dy2J) is an autosomal recessive disorder characterized by muscular dystrophy and dysmyelination of peripheral nerve. Biochemical characterization of dy2J mice revealed the expression of a mutant laminin alpha 2 chain with a smaller molecular weight in the basal lamina of striated muscle and peripheral nerve. DNA sequencing of the alpha 2 chain cDNA amplified by RT-PCR from dy2J mice identified a novel and predominant transcript with a 171 base in-frame deletion. We also confirmed an underlying splice donor site mutation in the alpha 2 chain gene of the dy2J mouse. Translation of this variant transcript would result in the expression of a truncated alpha 2 chain having a 57 amino acid deletion (residues 34-90) and a substitution of Gln91Glu in the N-terminal domain VI, which is presumed to be involved in self-aggregation of laminin heterotrimers. Thus, the mutant alpha 2 chain could disrupt the formation of the laminin network and lead to muscle cell degeneration. Our results provide a molecular basis of muscular dystrophy and dysmyelination of peripheral nerve.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blotting, Northern
  • DNA Primers
  • Demyelinating Diseases / genetics*
  • Gene Expression
  • Laminin / genetics*
  • Laminin / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Muscle, Skeletal / pathology
  • Muscular Dystrophy, Animal / genetics*
  • Peripheral Nerves / pathology
  • Polymerase Chain Reaction
  • RNA, Messenger / genetics
  • Sequence Deletion*


  • DNA Primers
  • Laminin
  • RNA, Messenger
  • laminin beta2