DP140 - A NOVEL 140-KDA CNS TRANSCRIPT FROM THE DYSTROPHIN LOCUS

We have identified a 7.5 kb transcript from the dystrophin locus which encodes a novel 140 kDa protein (Dp140). Based on immunoblotting Dp14 0 consists of the distal rod domain and C-terminus of 427 kDa dystroph in and is found throughout the CNS. This protein is transcribed from a n alternative promoter in the dystrophin locus upstream to exon 45. Th e unique 5' first exon is conserved between rat and human. The transcr ipt has a 1 kb 5' untranslated region, and the first methionine initia tion codon occurs in exon 51, predicting a protein of 140 kDa. Several studies report that Duchenne dystrophy patients with deletions in the exon 45-52 region have an increased incidence of cognitive impairment . Such deletions would affect expression of 427 kDa dystrophin and thi s shorter 140 kDa isoform but not the recently described smalt distal transcripts Dp116 or Dp71, suggesting particular importance to CNS fun ction.