DYSTROGLYCAN - BRAIN LOCALIZATION AND CHROMOSOME MAPPING IN THE MOUSE

Duchenne muscular dystrophy (DMD) is accompanied by varying degrees of mental retardation. The molecular basis for this is unknown, although at least four dystrophin transcripts regulated by specific promoters and undergoing elaborate splicing control are present in brain areas a ssociated with cognitive function. In muscle the absence of dystrophin causes instability of a dystrophin-associated protein complex (DAPC) linking the cytoskeleton to the extracellular matrix; this disruption is accompanied by muscle necrosis. The laminin-binding component of DA PC, dystroglycan, in contrast to other components of DAPC, has been fo und in brain homogenates. This suggests that the link between the memb rane cytoskeleton and extracellular matrix mediated by dystrophin-dyst roglycan may play a functional role in brain. We have cloned a mouse d ystroglycan partial cDNA and have mapped this gene in the mouse to chr omosome 9. Further, in situ hybridisation to mouse brain sections show s that the dystroglycan gene is expressed in relatively few structures and co-localises with dystrophin mRNA in hippocampus, dentate gyrus, olfactory bulb and Purkinje neurons but, surprisingly, not in the cort ex. Dystroglycan is also expressed in those brain areas where the dyst rophin-related protein (utrophin) is present. Our results provide a ba sis for a future characterisation of the role of dystrophin-dystroglyc an association in the brain.