Neurotrophic factors and their receptors: implications of genetic studies

The genes encoding each of the known neurotrophins and their receptors have been targeted in mice. As predicted by earlier studies, each mutation results in loss of specific classes of peripheral neurons. Apoptosis during the period of naturally occurring cell death appears to be responsible for many of these losses. In some cases, deficits may reflect earlier abnormalities in precursor proliferation, commitment or differentiation. Specific examples of abnormal target innervation and neuronal differentiation have been observed in these mutants, which are beginning to be used to address other postulated functions of neurotrophins, such as modulation of synaptic efficacy and plasticity.