TARGETED MUTATION IN THE NEUROTROPHIN-3 GENE RESULTS IN LOSS OF MUSCLE SENSORY NEURONS

Neurotrophin 3 (NT-3) is one of four related polypeptide growth factor s that share structural and functional homology to nerve growth factor (NGF). NT-3 and its receptor, called neurotrophic tyrosine kinase rec eptor type 3 (Ntrk3; also called TrkC), are expressed early and throug hout embryogenesis. We have inactivated the NT-3 gene in embryonic ste m (ES) cells by homologous recombination. The mutated allele has been transmitted through the mouse germ line, and heterozygote intercrosses have yielded homozygous mutant newborn pups. The NT3-deficient mutant s fail to thrive and exhibit severe neurological dysfunction, Analysis of mutant embryos uncovers loss of Ntrk3/TrkC-expressing sensory neur ons and abnormalities at early stages of sensory neuronal development. NT3-deficient mice will permit further study of the role of this neur otrophin in neural development.