MICE LACKING NERVE GROWTH-FACTOR DISPLAY PERINATAL LOSS OF SENSORY AND SYMPATHETIC NEURONS YET DEVELOP BASAL FOREBRAIN CHOLINERGIC NEURONS

Homologous recombination was utilized to generate mice with a deletion in the coding sequence of the nerve growth factor (NGF) gene. Animals homozygous for NGF disruption failed to respond to noxious mechanical stimuli, and histological analysis revealed profound cell loss in bot h sensory and sympathetic ganglia. Within dorsal root ganglia, effects of the mutation appeared to be restricted to small and medium peptide rgic neurons. These observations confirm the critical dependence of se nsory and sympathetic neurons on NGF and demonstrate that other neurot rophins are not able to compensate for the loss of NGF action on these cells. Examination of the central nervous system revealed that, in ma rked contrast with neurons of sensory and sympathetic ganglia, basal f orebrain cholinergic neurons differentiate and continue to express phe notypic markers for the life span of the null mutant mice. Thus, diffe rentiation and initial survival of central NGF-responsive neurons can occur in the absence of NGF.