Alternative dystrophin gene transcripts in golden retriever muscular dystrophy.
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.
Schatzberg
S J
SJ
College of Veterinary Medicine, North Carolina State University, Raleigh 27606, USA.
Anderson
L V
LV
Wilton
S D
SD
Kornegay
J N
JN
Mann
C J
CJ
Solomon
G G
GG
Sharp
N J
NJ
D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D015153:Blotting, Western; D004252:DNA Mutational Analysis; D004195:Disease Models, Animal; D004285:Dogs; D016189:Dystrophin / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D005091:Exons / Q000235:genetics; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000737:chemistry / Q000503:physiopathology; D009136:Muscular Dystrophies / Q000235:genetics*; D009137:Muscular Dystrophy, Animal / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000502:physiology
D000911:Antibodies, Monoclonal; D016189:Dystrophin