Apo-dystrophins (Dp140 and Dp71) and dystrophin splicing isoforms in developing brain.
PCR studies have shown that exons 71-74 are spliced out in most dystrophin mRNA transcripts in the brain. We have prepared new monoclonal antibodies against the syntrophin-binding region of dystrophin encoded by exons 73-74 and examined three protein products of the dystrophin gene in brain; the widely distributed Dp71, the recently discovered, brain-specific Dp140 and dystrophin itself. Exon 73-74 mAbs bound to all three proteins in brain and the extent of binding suggests that alternatively spliced dystrophins are less prominent at the protein level than predicted by PCR data. Dp140, unlike Dp71, was found to be present at much higher levels in foetal brain than in adult brain. If lack of functional Dp140 is the cause of the cognitive impairment in some Duchenne muscular dystrophy patients, this result suggests that the effects may occur early in development, which would reduce the options for therapeutic intervention.
Morris
G E
GE
MRIC Biotechnology Group, N.E. Wales Institute, Deeside, Clwyd, UK.
Simmons
C
C
Nguyen
T M
TM
D000328:Adult; D017398:Alternative Splicing; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D015153:Blotting, Western; D001921:Brain / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism*; D001923:Brain Chemistry; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000378:metabolism; D016189:Dystrophin / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D006801:Humans; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism*; D049411:Utrophin
D000911:Antibodies, Monoclonal; D003598:Cytoskeletal Proteins; D016189:Dystrophin; D008565:Membrane Proteins; D012333:RNA, Messenger; D049411:Utrophin