Alternative dystrophin gene transcripts in golden retriever muscular dystrophy

Muscle Nerve. 1998 Aug;21(8):991-8. doi: 10.1002/(sici)1097-4598(199808)21:8<991::aid-mus2>3.0.co;2-0.

Abstract

Golden retriever muscular dystrophy (GRMD), the canine model of Duchenne muscular dystrophy (DMD), is caused by a splice site mutation in the dystrophin gene. This mutation predicts a premature termination codon in exon 8 and a peptide that is 5% the size of normal dystrophin. Western blot analysis of skeletal muscle from GRMD dogs reveals a slightly truncated 390-kD protein that is approximately 91% the size of normal dystrophin. This 390-kD dystrophin suggests that GRMD dogs, like some DMD patients, employ a mechanism to overcome their predicted frameshift. Reverse-transcriptase polymerase chain reaction on GRMD muscle has revealed two in-frame dystrophin transcripts which lack either exons 3-9 or exons 5-12. Both transcripts could be translated into a dystrophin protein of approximately 390 kD. An understanding of how truncated dystrophin is produced in GRMD may allow this mechanism to be manipulated toward a potential therapy for DMD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / genetics*
  • Animals
  • Antibodies, Monoclonal
  • Base Sequence
  • Blotting, Western
  • DNA Mutational Analysis
  • Disease Models, Animal
  • Dogs
  • Dystrophin / analysis
  • Dystrophin / genetics*
  • Dystrophin / immunology
  • Exons / genetics
  • Molecular Sequence Data
  • Muscle, Skeletal / chemistry
  • Muscle, Skeletal / physiopathology
  • Muscular Dystrophies / genetics*
  • Muscular Dystrophy, Animal / genetics*
  • Phenotype
  • Polymerase Chain Reaction
  • Transcription, Genetic / physiology

Substances

  • Antibodies, Monoclonal
  • Dystrophin