ISOFORMS OF AGRIN ARE WIDELY EXPRESSED IN THE DEVELOPING RAT AND MAY FUNCTION AS PROTEASE INHIBITORS

The agrin family of extracellular matrix proteins may be important in the formation of the neuromuscular junction. Using in situ hybridizati on with a probe recognizing all agrin isoforms, we demonstrate that it is widely expressed during mammalian embryogenesis. In the developing rat, particularly high levels of expression are found in the dorsal r oot and cranial ganglia, gut, whisker rudiments, penis, snout, teeth, retina, hippocampus, cerebral cortex and the lining of brain ventricle s. Functional analysis of the recombinant rat protein shows that it is a potent inhibitor of the proteases trypsin, chymotrypsin and plasmin but not thrombin or the plasminogen activators. We conclude that agri n and its isoforms may play multiple roles in mammalian development in cluding the regulation of proteolysis in the extracellular matrix.