EXPRESSION OF UTROPHIN AND ITS MESSENGER-RNA IN DENERVATED MDX MOUSE MUSCLE

Utrophin is a large cytoskeletal protein which shows high homology to dystrophin. In contrast to the sarcolemmal distribution of dystrophin, utrophin accumulates at the postsynaptic membrane of the neuromuscula r junction. Because of its localization within this compartment of mus cle fibers, expression of utrophin may be significantly influenced by the presence of the motor nerve. We tested this hypothesis by denervat ing muscles of mdx mouse and monitoring levels of utrophin and its mRN A by immunofluorescence, immunoblotting and RT-PCR. A significant incr ease in the number of utrophin positive fibers was observed by immunof luorescence 3 to 21 days after sectioning of the sciatic nerve. Quanti tative analyses of utrophin and its transcripts in hindlimb muscles de nervated for two weeks showed only a moderate increase in the levels o f both utrophin (similar to 2-fold) and its transcript (similar to 60 to 90%), The present data suggest that although utrophin is a componen t of the postsynaptic membrane, its neural regulation is distinct from that of the acetylcholine receptor.