Severe sensory and sympathetic neuropathies in mice carrying a disrupted Trk/NGF receptor gene (original) (raw)

Nature volume 368, pages 246–249 (1994)Cite this article

Abstract

NERVE growth factor (NGF) induces neurite outgrowth and promotes survival of embryonic sensory and sympathetic neurons in culture1,2. In vivo, NGF decreases the extent of naturally occurring cell death in developing sympathetic ganglia and protects cholinergic neurons of the basal forebrain and caudatoputamen1-3. NGF interacts with the low-affinity p75 receptor and with Trk, a receptor tyrosine kinase encoded by the trk proto-oncogene4,5. 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.

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Authors and Affiliations

  1. Department of Molecular Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey, 08543-4000, USA
    Richard J. Smeyne, Rüdiger Klein, Linda K. Long, Sherri Bryant, Anne Lewin, Sergio A. Lira & Mariano Barbacid
  2. Differentiation Programme, European Molecular Biology Laboratory, 69012, Heidelberg, Germany
    Rüdiger Klein & Andreas Schnapp

Authors

  1. Richard J. Smeyne
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  2. Rüdiger Klein
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  3. Andreas Schnapp
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  4. Linda K. Long
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  5. Sherri Bryant
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  6. Anne Lewin
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  7. Sergio A. Lira
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  8. Mariano Barbacid
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Smeyne, R., Klein, R., Schnapp, A. et al. Severe sensory and sympathetic neuropathies in mice carrying a disrupted Trk/NGF receptor gene.Nature 368, 246–249 (1994). https://doi.org/10.1038/368246a0

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