APO-DYSTROPHIN-1 AND APO-DYSTROPHIN-2, PRODUCTS OF THE DUCHENNE MUSCULAR-DYSTROPHY LOCUS - EXPRESSION DURING MOUSE EMBRYOGENESIS AND IN CULTURED-CELL LINES

Two promoters in the distal half of the Duchenne Muscular Dystrophy ge ne drive transcription of mRNAs which have novel first exons and encod e the shortened forms of dystrophin, apo-dystrophin-1 (Dp71) and apody strophin-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 co nfined to peripheral nerve and brain. We have isolated and sequenced t he 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 seque nces at the 5' ends of apo-dystrophin-1 and apo-dystrophin-2 we have d etermined the expression of these two mRNAs during mouse embryonic dev elopment by RNA in situ hybridization. In contrast to full-length dyst rophin, neither of these short dystrophin transcripts appear before or ganogenesis is well established. Apo-dystrophin-1 mRNA is detected in midline cells of the ventral neural tube and later, in the ependymal c ells lining the ventricles of the brain. These results suggest that ap o-dystrophin-1 mRNA is associated with glial cells in the CNS. Apo-dys trophin-1 transcripts are also abundant in the teeth primordia through out their development. In contrast apo-dystrophin-2 mRNA is largely un detectable during development, although transcripts are seen in the ne wborn brain. Western blots of late human fetal tissue extracts confirm that apo-dystrophin-2 is most abundant in brain and analysis of RNA a nd protein in cultured cell lines reveal expression of apo-dystrophin- 2 and apo-dystrophin-2 in glioma cells.