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

L Aigner; S Arber; J P Kapfhammer; T Laux; C Schneider; F Botteri; H R Brenner; P Caroni

doi:10.1016/0092-8674(95)90168-x

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

Cell. 1995 Oct 20;83(2):269-78. doi: 10.1016/0092-8674(95)90168-x.

Authors

L Aigner¹, S Arber, J P Kapfhammer, T Laux, C Schneider, F Botteri, H R Brenner, P Caroni

Affiliation

¹ Friedrich Miescher Institute, Basel, Switzerland.

PMID: 7585944
DOI: 10.1016/0092-8674(95)90168-x

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

GAP-43 Protein
Growth Substances
Membrane Glycoproteins
Nerve Tissue Proteins
Recombinant Proteins
Protein Kinase C