Overexpression of the neural growth-associated protein GAP-43 induces nerve sprouting in the adult nervous system of transgenic mice

• Published in: Cell Vol. 83; no. 2; pp. 269 - 278
• Main Authors: Aigner, Ludwig, Arber, Silvia, Kapfhammer, Josef P., Laux, Thorsten, Schneider, Corinna, Botteri, Florence, Brenner, Hans-Ruedi, Caroni, Pico
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20-10-1995
• Subjects: Animals; Chickens - genetics; GAP-43 Protein; Growth Substances - genetics; Growth Substances - metabolism; Growth Substances - pharmacology; Hippocampus - cytology; Hippocampus - drug effects; Hippocampus - growth & development; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Membrane Glycoproteins - pharmacology; Mice; Mice, Transgenic; Motor Activity - genetics; Motor Neurons - cytology; Motor Neurons - drug effects; Mutagenesis; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Nerve Tissue Proteins - pharmacology; Nervous System - drug effects; Nervous System - growth & development; Neurites - drug effects; Neurites - ultrastructure; Neuromuscular Junction - cytology; Neuromuscular Junction - drug effects; Neuromuscular Junction - growth & development; Neuronal Plasticity - genetics; Phosphorylation; Protein Kinase C - metabolism; Recombinant Proteins - metabolism; Recombinant Proteins - pharmacology; Seizures - genetics
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/0092-8674(95)90168-X

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 transgenic mice. Such mice showed striking spontaneous nerve sprouting at the neuromuscular junction and in the terminal field of hippocampal mossy fibers. In control mice, these nerve fibers did not express GAP-43, and did not sprout spontaneously. Lesion-induced nerve sprouting and terminal 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 GAP-43 as an intrinsic presynaptic determinant for neurite outgrowth and plasticity.