Homologous recombination was utilized to generate mice wlth a deletion in the coding seguence of the nerve growth factor (NGF) gene. Animals homozygous for NGF disruption failed to respond to noxious mechanlcal stlmuli, and hlstologlcal analysis revealed profound cell loss in both sensory and sympathetic ganglia. Wlthin dorsal root ganglia, effects of the mutatlon appeared to bs restricted to small and medium pepti~ ic neurons. These observations conflrm the critical dependence of sensory and sympathetic neurons on NGF and demonstrate that other neurotrophins am not able to compensate for the loss of NGF actlon on these cells. Examination of the central nervous system revealed that, in marked contmst wlth neurons of sensory and sympathetic ganglia, basal fombmln choiinerglc neurons dlfferentlae and continue to express phenotypic markers for the life span of the null mutant mim. Thus, dlfferentiatlon and inltial survival of central NGF-msponslve neurons can occur in the absence of NGF. lntroductlon

Nerve growth factor (NGF) is the first described member of a family of proteins known as the neurotrophins, which are believed to influence the differentiation and survival of neurons in the developing nervous system (Levi-Montalcini, 1987; Thoenen and Barde, 1980; Thoenen, 1991). Overwhelming evidence for the role of NGF in promoting the survival of neurons of sympathetic and sensory ganglia comes from a series of in vitro and in vivo studies initiated over 40 years ago (see Levi-Montalcini, 1987; Hamburger, 1993). During the past decade, an increasing body of evidence indicates that NGF may also play a role in the brain to support the survival or function of the basal