TARGETED DISRUPTION OF THE BDNF GENE PERTURBS BRAIN AND SENSORY NEURON DEVELOPMENT BUT NOT MOTOR-NEURON DEVELOPMENT

Brain-derived neurotrophic factor (BDNF), a neurotrophin, enhances the survival and differentiation of several classes of neurons in vitro. To determine its essential functions, we have mutated the BDNF gene. M ost homozygote mutants die within 2 days after birth, but a fraction l ive for 2-4 weeks. These develop symptoms of nervous system dysfunctio n, including ataxia. The BDNF mutant homozygotes have substantially re duced numbers of cranial and spinal sensory neurons. Although their ce ntral nervous systems show no gross structural abnormalities, expressi on of neuropeptide Y and calcium-binding proteins is altered in many n eurons, suggesting they do not function normally. In contrast with mic e lacking the BDNF receptor TrkB, motor neurons appear normal in the B DNF mutant.