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The p75 neurotrophin receptor influences NT-3 responsiveness of sympathetic neurons in vivo

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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Figure 1: Comparison of superior cervical ganglia (SCG) size from the four different genotypes of p75NTR/NGF mice.
Figure 2: Cresyl violet stained SCG paraffin sections from the four different genotypes of p75NTR/NGF mice.
Figure 3: Lack of wild-type p75NTR does not alter sympathetic neuron number.
Figure 4: SCG neurons become sensitive to NGF gene dosage between E16.5 and P0.
Figure 5: NT-3 can compensate for the loss of one allele of NGF in p75NTR–/– NGF+/– mice.

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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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Correspondence to Christine Brennan.

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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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