Abstract
Nerve growth factor (NGF) was the first neurotropin isolated. In vitro it supports both neuronal survival and process outgrowth. This chapter presents a study in which immunohistochemical analyses of the footpad skin of mutant mice revealed markedly decreased sensory innervation by calcitonin gene-related peptide- and substance P-immunoreactive fibers. The defective innervation was correlated with loss of heat sensitivity, and associated with the development of ulcers in the distal extremities. Complicated by secondary bacterial infection, the ulcers progressed to toe nail and hair loss. Crossing a human transgene encoding p75NGFR into the mutant animals rescued the absent heat sensitivity and the occurrence of skin ulcers, and increased the density of neuropeptide-immunoreactive sensory innervation of footpad skin. The mutation in the gene encloding p75NGFR did not decrease the size of sympathetic ganglia or the density of sympathetic innervation of the iris or salivary gland. These results show that p75NGFR plays an important role in the development and function of sensory neurons.
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