The p75 neurotrophin receptor influences NT-3 responsiveness of sympathetic neurons in vivo.
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.
Neural Development Section, National Institutes of Neurological Disorders and Stroke, National Institutes of Health, 36 Convent Dr., Bldg. 36/Rm. 2B08, Bethesda, Maryland 20892-4064, USA. cbrennan@codon.nih.gov
C
C
Brennan
K
K
Rivas-Plata
S C
SC
Landis
D000222:Adaptation, Physiological; D000483:Alleles; D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count; D005728:Ganglia, Sympathetic / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009414:Nerve Growth Factors / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D020933:Neurotrophin 3; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000502:physiology*
D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor