OVEREXPRESSION OF THE NEURAL GROWTH-ASSOCIATED PROTEIN GAP-43 INDUCESNERVE SPROUTING IN THE ADULT NERVOUS-SYSTEM OF TRANSGENIC MICE

Regulation of neurite outgrowth and structural plasticity may involve the expression of intrinsic determinants controlling growth competence . We have tested this concept by targeting constitutive expression of the growth-associated protein GAP-43 to the neurons of adult transgeni c mice. Such mice showed striking spontaneous nerve sprouting at the n euromuscular junction and in the terminal field of hippocampal messy f ibers. In control mice, these nerve fibers did not express GAP-43, and did not sprout spontaneously. Lesion-induced nerve sprouting and term inal arborization during reinnervation were greatly potentiated in GAP -43-overexpressing mice. A mutant GAP-43 that cannot be phosphorylated by PKC had reduced sprout-promoting activity. The results establish G AP-43 as an intrinsic presynaptic determinant for neurite outgrowth an d plasticity.