LIMB PROPRIOCEPTIVE DEFICITS WITHOUT NEURONAL LOSS IN TRANSGENIC MICEOVEREXPRESSING NEUROTROPHIN-3 IN THE DEVELOPING NERVOUS-SYSTEM

The role of neurotrophin-3 (NT3) during sensory neuron development was investigated in transgenic mice overexpressing NT3 under the control of the promoter and enhancer regions of the nestin gene, an intermedia te filament gene widely expressed in the developing nervous system, Mo st of these mice died during the first postnatal day, and all showed s evere limb ataxia suggestive of limb proprioceptive dysfunction, Traci ng and histological analyses revealed a complete loss of spindles in l imb muscles, absence of peripheral and central Ia projections, and lac k of cells immunoreactive to parvalbumin in the dorsal root ganglion ( DRG). Despite these deficits, there was no neuronal loss in the DRG of these mice, At birth, transgenic DRG showed increased neuron numbers, and displayed a normal proportion of neurons expressing substance P, calcitonin generelated peptide and the NT3 receptor trkC, Transgenic d orsal roots exhibited an increased number of axons at birth, indicatin g that all sensory neurons in transgenic mice projected to the dorsal spinal cord, Despite the absence of central Ia afferents reaching moto rneurons, several sensory fibers were seen projecting towards ectopic high levels of NT3 in the midline of transgenic spinal cords, These fi ndings suggest novel roles for NT3 in differentiation of proprioceptiv e neurons, target invasion and formation of Ia projections which are i ndependent from its effects on neuronal survival.