The muscular dystrophy with myositis (mdm) mouse mutation disrupts a skeletal muscle-specific domain of titin

Genomics. 2002 Feb;79(2):146-9. doi: 10.1006/geno.2002.6685.


Muscular dystrophy with myositis (mdm) is a recessive mouse mutation that causes severe and progressive muscular degeneration. Here we report the identification of the mdm mutation as a complex rearrangement that includes a deletion and a LINE insertion in the titin (Ttn) gene. Mutant allele-specific splicing results in the deletion of 83 amino acids from the N2A region of TTN, a domain thought to bind calpain-3 (CAPN3) the product of the human limb-girdle muscular dystrophy type 2A (LGMD2A) gene. The Ttn(mdm) mutant mouse may serve as a model for human tibial muscular dystrophy, which maps to the TTN locus at 2q31 and shows a secondary reduction of CAPN3 similar to that observed in mdm skeletal muscle. This is the first demonstration that a mutation in Ttn is associated with muscular dystrophy and provides a novel animal model to test for functional interactions between TTN and CAPN3.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calpain / metabolism
  • Chromosome Mapping
  • Cloning, Molecular
  • Connectin
  • Gene Deletion
  • Ligands
  • Mice
  • Mice, Inbred C57BL
  • Muscle Proteins / chemistry
  • Muscle Proteins / genetics*
  • Muscle, Skeletal / physiopathology
  • Muscular Dystrophy, Animal / genetics*
  • Mutagenesis, Insertional
  • Myositis / genetics*
  • Peptide Fragments
  • Protein Binding
  • Protein Kinases / chemistry
  • Protein Kinases / genetics*
  • Protein Structure, Tertiary


  • Connectin
  • Ligands
  • Muscle Proteins
  • Peptide Fragments
  • TTN protein, human
  • Protein Kinases
  • Calpain
  • Capn3 protein, mouse
  • calpain p94