Severe sensory and sympathetic neuropathies in mice carrying a disrupted Trk/NGF receptor gene.
Publication/Presentation Date
3-17-1994
Abstract
Nerve growth factor (NGF) induces neurite outgrowth and promotes survival of embryonic sensory and sympathetic neurons in culture. In vivo, NGF decreases the extent of naturally occurring cell death in developing sympathetic ganglia and protects cholinergic neurons of the basal forebrain and caudatoputamen. NGF interacts with the low-affinity p75 receptor and with Trk, a receptor tyrosine kinase encoded by the trk proto-oncogene. To study the role of Trk in vivo, we have ablated the gene in embryonic stem cells by homologous recombination. Mice lacking Trk have severe sensory and sympathetic neuropathies and most die within one month of birth. They have extensive neuronal cell loss in trigeminal, sympathetic and dorsal root ganglia, as well as a decrease in the cholinergic basal forebrain projections to the hippocampus and cortex. These findings demonstrate that Trk is the primary mediator of the trophic actions of NGF in vivo and that this signalling pathway plays a crucial role in the development of both the peripheral and the central nervous systems.
Volume
368
Issue
6468
First Page
246
Last Page
249
ISSN
0028-0836
Published In/Presented At
Smeyne, R. J., Klein, R., Schnapp, A., Long, L. K., Bryant, S., Lewin, A., Lira, S. A., & Barbacid, M. (1994). Severe sensory and sympathetic neuropathies in mice carrying a disrupted Trk/NGF receptor gene. Nature, 368(6468), 246–249. https://doi.org/10.1038/368246a0
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
8145823
Department(s)
Administration and Leadership
Document Type
Article