An error in dystrophin mRNA processing in golden retriever muscular dystrophy, an animal homologue of Duchenne muscular dystrophy.
Golden retriever muscular dystrophy (GRMD) is a spontaneous, X-linked, progressively fatal disease of dogs and is also a homologue of Duchenne muscular dystrophy (DMD). Two-thirds of DMD patients carry detectable deletions in their dystrophin gene. The defect underlying the remaining one-third of DMD patients is undetermined. Analysis of the canine dystrophin gene in normal and GRMD dogs has failed to demonstrate any detectable loss of exons. Here, we have demonstrated a RNA processing error in GRMD that results from a single base change in the 3' consensus splice site of intron 6. The seventh exon is then skipped, which predicts a termination of the dystrophin reading frame within its N-terminal domain in exon 8. This is the first example of dystrophin deficiency caused by a splice-site mutation.
Sharp
N J
NJ
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
Kornegay
J N
JN
Van Camp
S D
SD
Herbstreith
M H
MH
Secore
S L
SL
Kettle
S
S
Hung
W Y
WY
Constantinou
C D
CD
Dykstra
M J
MJ
Roses
A D
AD
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D004285:Dogs / Q000235:genetics / Q000378:metabolism; D016189:Dystrophin / Q000737:chemistry / Q000235:genetics*; D005091:Exons / Q000235:genetics; D007438:Introns / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009137:Muscular Dystrophy, Animal / Q000503:physiopathology*; D009154:Mutation / Q000235:genetics; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*
D016189:Dystrophin; D012333:RNA, Messenger