The large DMD gene encodes a group of dystrophin proteins in brain and retina, produced from multiple promoters and alternative splicing events. Dystrophins are core components of different scaffolding complexes in distinct cell types. Their absence may thus alter several cellular pathways, which might explain the heterogeneous genotype–phenotype relationships underlying central comorbidities in Duchenne muscular dystrophy (DMD). However, the cell-specific expression of dystrophins and associated proteins (DAPs) is still largely unknown. The present study provides a first RNA-Seq-based reference showing tissue- and cell-specific differential expression of dystrophins, splice variants and DAPs in mouse brain and retina. We report that a cell type may express several dystrophin complexes, perhaps due to expression in separate cell subdomains and/or subpopulations, some of which with differential expression at different maturation stages. We also identified new splicing events in addition to the common exon-skipping events. These include a new exon within intron 51 (E51b) in frame with the flanking exons in retina, as well as inclusions of intronic sequences with stop codons leading to the presence of transcripts with elongated exons 40 and/or 41 (E40e, E41e) in both retina and brain. PCR validations revealed that the new exons may affect several dystrophins. Moreover, immunoblot experiments using a combination of specific antibodies and dystrophin-deficient mice unveiled that the transcripts with stop codons are translated into truncated proteins lacking their C-terminus, which we called N-Dp427 and N-Dp260. This study thus uncovers a range of new findings underlying the complex neurobiology of DMD.

J. Neurochem. (2011) 119, 697–707. Dp71 has an important role in the central nervous system. To better understand the function of Dp71 domains in neuronal differentiation, PC12 cells were stably transfected with a dystrophin mutant, Dp71Δ_78‐79, which lacks exons 78 and 79. Based on the percentage of cells bearing neurites and neurite length analyses, we found that cells stably expressing Dp71Δ_78‐79 (PC12‐C11) differentiate more efficiently than non‐transfected cells. While wild‐type cells reach their maximum differentiation 9–12 days after initiating the differentiation process, the PC12‐C11 cells reach differentiation in 4–6 days. Protein expression analysis showed a down‐regulation of Dp71a and an up‐regulation of Dp71ab and/or Up71, β‐dystroglycan and neuron‐specific enolase in undifferentiated and in neural growth factor differentiated PC12‐C11 cells. No change was observed in the expression of Grb2 and Up400. The subcellular localization of Dp71Δ_78‐79 was in the cell periphery, and there was no change in localization during the differentiation process, which was also observed throughout the neurite extensions.