DIFFERENTIAL EXPRESSION OF SYNTROPHINS AND ANALYSIS OF ALTERNATIVELY SPLICED DYSTROPHIN TRANSCRIPTS IN THE MOUSE-BRAIN

Expression of syntrophin genes, encoding members of the dystrophin-ass ociated protein complex, was studied in the mouse brain, In the hippoc ampal formation there is distinctive co-localization of specific syntr ophins with certain dystrophin isoforms in neurons, e.g. alpha(1)-synt rophin with the C-dystrophin in CA regions and beta(2)-syntrophin with the G-dystrophin in the dentate gyrus. Expression of the alpha(1)-syn trophin is predominant in CA regions and the olfactory bulb and it is also present in the cerebral cortex and the dentate gyrus. The beta(2) -syntrophin mRNA is most abundant in the dentate gyrus and is also evi dent in the pituitary, the cerebral cortex and in Ammon's horn and in traces in the caudate putamen. The choroid plexus was labelled by both alpha(1)- and beta(2)-syntrophin-specific probes. The expression of s yntrophins in the brain correlates with expression of dystrophins and dystroglycan. There are brain areas such as the cerebral cortex where several different syntrophins and dystrophins are expressed together, Syntrophin expression co-localizes with utrophin in the choroid plexus and caudate putamen, Finally, no syntrophin was detected in the cereb ellar Purkinje cells where the specific dystrophin isoform (P-type) is present, This specific distribution of syntrophins in the brain is pa rticularly interesting, as muscle syntrophin interacts with neuronal n itric oxide synthase. This may suggest that the dystrophin-associated protein complex may be involved in synaptic organisation and signal tr ansduction machinery in both muscle and neurons. The dystrophin isofor m, with exons 71-74 spliced out and hence lacking syntrophin binding s ites, had been believed to be predominant in the brain, but our analys es using in situ hybridization, S1 nuclease protection and the semi-qu antitative polymerase chain reaction revealed that this alternatively spliced mRNA is a minor, tow abundance form in the brain.