DISRUPTION OF THE NEURATROPHIN-3 RECEPTOR GENE TRKC ELIMINATES LA MUSCLE AFFERENTS AND RESULTS IN ABNORMAL MOVEMENTS

THE trkC gene(1,2) is expressed throughout the mammalian nervous syste m(3-5) and encodes a series of tyrosine protein kinase isoforms that s erve as receptors for neurotrophin-3 (NT3), a member of the nerve grow th factor (NGF) family of neurotrophic factors(2,6-8). One of these is oforms, gp145(trkC)/TrkC K1, mediates the trophic properties of NT3 in cultured Cells(2,6-8). Here we show that homozygous mice defective fo r TrkC tyrosine protein kinase receptors lack Ia muscle afferent proje ctions to spinal motor neurons and have fewer large myelinated axons i n the dorsal root and posterior columns of the spinal cord. These mice display abnormal movements and postures, indicating that NT3/TrkC-dep endent sensory neurons may play a primary role in proprioception, the sense of position and movement of the limbs.