Severe peripheral sensory neuron loss and modest motor neuron reduction in mice with combined deficiency of brain-derived neurotrophic factor, neurotrophin 3 and neurotrophin 4/5.

Neurotrophins are a family of structurally and functionally related proteins that regulate neuronal survival during development. In the peripheral nervous system (PNS), both in vitro and in vivo studies have shown that neurotrophins are potent factors for the survival of various sensory neurons and sympathetic neurons. However, it is not clear whether all PNS neurons are neurotrophin-dependent. In the central nervous system (CNS), studies using injury models show that neurotrophins promote the survival of CNS neurons. But mice lacking individual neurotrophins or a combination of BDNF and NT4 did not show significant CNS neuronal loss. Here we derived mice lacking three neurotrophins, brain-derived growth factor (BDNF), neurotrophin-3 (NT3), and neurotrophin-4 (NT4) to study the effect of triple neurotrophin deficiency on peripheral and central neurons. These triple-deficient mice did not nurse and died within 12 hours after birth. Neuronal cell counts showed that triple mutant pups lacked most of their peripheral sensory neurons and had a statistically significant reduction of motor neurons in several motor nuclei. Our results suggest that neurotrophins are essential for the survival of most peripheral sensory neurons and affect the survival of a small portion of motor neurons during embryogenesis.