EXPRESSION OF NGF IN SYMPATHETIC NEURONS LEADS TO EXCESSIVE AXON OUTGROWTH FROM GANGLIA BUT DECREASED TERMINAL INNERVATION WITHIN TISSUES

The effects of nerve growth factor (NGF) on sympathetic axon growth we re investigated by generating transgenic mice in which the beta subuni t of NGF was expressed in sympathetic neurons using the human dopamine beta-hydroxylase (DBH) promoter. In DBH-NGF mice, the sympathetic tru nk and nerves growing to peripheral tissues were enlarged and containe d an increased number of sympathetic fibers. Although sympathetic axon s reached peripheral tissues, terminal sympathetic innervation within tissues was decreased in DBH-NGF mice. This effect could be reversed i n the pancreas by overexpression of NGF in pancreatic islets. The obse rvations are consistent with a model in which NGF gradients are not re quired to guide sympathetic axons to their targets, but are required f or the establishment of the normal density and pattern of sympathetic innervation within target tissues.