The low-affinity neurotrophin receptor p75 regulates the function but not the selective survival of specific subpopulations of sensory neurons.
Mice with a targeted deletion of the low-affinity neurotrophin receptor p75 (p75-/-) exhibit a 50% loss of large- and small-diameter sensory neurons in the dorsal root ganglion. Using neurophysiological recording techniques, we now show that p75 is not required for the survival of specific, functionally defined subpopulations of sensory neurons. Rather, p75-/- mice exhibit losses of neurons that subserve nociceptive as well as non-nociceptive functions. The receptive properties of large myelinated afferent fibers were normal in p75-/- mice. However, the receptive properties of subpopulations of afferent fibers with thin myelinated or unmyelinated axons were strikingly impaired in mice lacking p75. Furthermore, the presence of p75 is required for normal mechanotransduction in C fibers and D-hair receptors and normal heat sensitivity in A-fiber nociceptors.
Stucky
C L
CL
Department of Neurology, University of Würzburg, D-97080 Würzburg, Germany.
Koltzenburg
M
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003080:Cold Temperature; D004558:Electric Stimulation; D004594:Electrophysiology; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006720:Homozygote; D006358:Hot Temperature; D008297:Male; D008465:Mechanoreceptors / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D016296:Mutagenesis / Q000502:physiology; D009414:Nerve Growth Factors / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D009475:Neurons, Afferent / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology; D020933:Neurotrophin 3; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D012684:Sensory Thresholds / Q000187:drug effects / Q000502:physiology
C495040:Gdnf protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D020933:Neurotrophin 3; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; C073922:neurotrophin 4