Studies on the physiological role of brain-derived neurotrophic factor and neurotrophin-3 in knockout mice.

Brain-derived neurotrophic factor and neurotrophin-3 deficient mice were generated by gene targeting. The analysis of these mice has led to the characterization of their role in the survival of neurons in the peripheral nervous system. NT-3 deficient mice displayed severe movement defects and most died shortly after birth. The mutation causes loss of substantial portions of cranial and spinal peripheral sensory and sympathetic neurons. Significantly, spinal proprioceptive afferents and their peripheral sense organs (muscle spindles and Golgi tendon organs) were completely absent in homozygous mutant mice. BDNF deficient mice displayed deficiencies in coordination and balance. Excessive loss of neurons was detected in most of the peripheral sensory ganglia examined, but the survival of sympathetic neurons was not affected. The most marked reduction of neurons was observed in the vestibular ganglion, leading to a loss of innervation of the sensory epithelia of the vestibular compartments of the inner ear.