Abstract
To determine the role of the p75 neurotrophin receptor (p75NTR) in sympathetic neuron development, we crossed transgenic mice with mutations in p75NTR, nerve growth factor (NGF) and neurotrophin-3 (NT-3). Neuron number is normal in sympathetic ganglia of adult p75NTR–/– mice. Mice heterozygous for a NGF deletion (NGF+/–) have 50% fewer sympathetic neurons. In the absence of p75NTR (p75NTR–/– NGF+/–), however, neuron number is restored to wild-type levels. When NT-3 levels are reduced (p75NTR–/– NGF+/– NT3+/–), neuron number decreases compared to p75NTR–/– NGF+/– NT3+/+. Thus, without p75NTR, NT3 substitutes for NGF, suggesting that p75 alters the neurotrophin specificity of TrkA in vivo.
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Acknowledgements
The authors thank Heidi Philips at Genentech for providing the NGF-deficient mice, Louis Reichardt at the University of California, San Francisco for providing NT-3-deficient mice, Charles Gerfen at NIMH for use of the Neurolucida image analysis system, and Nicole Francis, Guy Guidry and James Coulombe for discussions and reading of the manuscript. The NINDS intramural research program supported this work.
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Brennan, C., Rivas-Plata, K. & Landis, S. The p75 neurotrophin receptor influences NT-3 responsiveness of sympathetic neurons in vivo. Nat Neurosci 2, 699–705 (1999). https://doi.org/10.1038/11158
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DOI: https://doi.org/10.1038/11158
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