title: Apo-dystrophin-1 and apo-dystrophin-2, products of the Duchenne muscular dystrophy locus: expression during mouse embryogenesis and in cultured cell lines.
abstract: Two promoters in the distal half of the Duchenne Muscular Dystrophy gene drive transcription of mRNAs which have novel first exons and encode the shortened forms of dystrophin, apo-dystrophin-1 (Dp71) and apo-dystrophin-2 (Dp116). Apo-dystrophin-1 has a G + C rich promoter and is expressed in a wide range of cell types, whilst apo-dystrophin-2 is confined to peripheral nerve and brain. We have isolated and sequenced the unique 5' exon of rat apo-dystrophin-2 mRNA. Conceptual translation of this sequence indicates that apo-dystrophin-2 contains a unique 23 amino acid terminal peptide. Using specific probes derived from sequences at the 5' ends of apo-dystrophin-1 and apo-dystrophin-2 we have determined the expression of these two mRNAs during mouse embryonic development by RNA in situ hybridization. In contrast to full-length dystrophin, neither of these short dystrophin transcripts appear before organogenesis is well established. Apo-dystrophin-1 mRNA is detected in midline cells of the ventral neural tube and later, in the ependymal cells lining the ventricles of the brain. These results suggest that apo-dystrophin-1 mRNA is associated with glial cells in the CNS. Apo-dystrophin-1 transcripts are also abundant in the teeth primordia throughout their development. In contrast apo-dystrophin-2 mRNA is largely undetectable during development, although transcripts are seen in the newborn brain. Western blots of late human fetal tissue extracts confirm that apo-dystrophin-2 is most abundant in brain and analysis of RNA and protein in cultured cell lines reveal expression of apo-dystrophin-1 and apo-dystrophin-2 in glioma cells.
authors.affiliation: MRC, Human Biochemical Genetics Group, University College London, UK.
authors.forename: J N
authors.initials: JN
authors.lastname: Schofield
authors.forename: D J
authors.initials: DJ
authors.lastname: Blake
authors.forename: C
authors.initials: C
authors.lastname: Simmons
authors.forename: G E
authors.initials: GE
authors.lastname: Morris
authors.forename: J M
authors.initials: JM
authors.lastname: Tinsley
authors.forename: K E
authors.initials: KE
authors.lastname: Davies
authors.forename: Y H
authors.initials: YH
authors.lastname: Edwards
mesh_terms: D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000196:embryology; D002460:Cell Line; D002478:Cells, Cultured; D016189:Dystrophin / Q000031:analogs & derivatives* / Q000235:genetics; D005314:Embryonic and Fetal Development / Q000235:genetics*; D015870:Gene Expression / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009136:Muscular Dystrophies / Q000235:genetics*; D051381:Rats
chemical_list: C484258:DMD protein, human; C090839:Dmd protein, rat; D016189:Dystrophin; C085339:apo-dystrophin 1