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

To determine the role of the p75 neurotrophin receptor (p75(NTR)) in sympat hetic neuron development, we crossed transgenic mice with mutations in p75( NTR), nerve growth factor (NGF) and neurotrophin-3 (NT-3). Neuron number is normal in sympathetic ganglia of adult p75(NTR-/-) mice. Mice heterozygous for a NGF deletion (NGF(+/-)) have 50% fewer sympathetic neurons. In the a bsence of p75(NTR) (P75(NTR-/-) NGF(+/-)), however, neuron number is restor ed to wild-type levels. When NT-3 levels are reduced (p75(NTR-/-) NGF(+/-) NT3(+/-)), neuron number decreases compared to p75(NTR-/-) NGF(+/-) NT3(+/). Thus, without p75(NTR), NT3 substitutes for NGF, suggesting that p75 alt ers the neurotrophin specificity of TrkA in vivo.