Analysis of Cutaneous Sensory Neurons in Transgenic Mice Lacking the Low Affinity Neurotrophin Receptor p75

Abstract

Mice with a targeted mutation of the p75 low affinity neurotrophin receptor display smaller peripheral nerves and dorsal root ganglia. Here we show that transgenic mice have a significant elevation of thresholds to noxious mechanical and heat stimuli compared with p75+/+ control mice. Immunocytochemical analysis using antibodies against PGP 9.5 (a panaxonal marker) and calcitonin gene related peptide (CGRP, which labels peptidergic neurons) showed a reduction to 73% and 54%, respectively, of the epidermal innervation density. However, analysis of the cell size distribution of toluidine blue-stained dorsal root ganglia showed no selective loss of neurons of particular diameters. Moreover, the neurochemical profile of dorsal root ganglia cells as defined by trkA, CGRP, IB4 and RT97 immunostaining revealed no significant differences in comparison with p75+/+ animals. Staining of the dorsal horn of the spinal cord for CGRP and IB4 was also normal in p75-/- animals. Taking into account a previously reported loss of approximately 50% dorsal root ganglion neurons, we conclude that all types of sensory neurons are equally depleted in p75-/- mice and that the absence of p75 impedes the development of more than one neuronal subtype.