Open AccessTargeted mutation in the neurotrophin-3 gene results in loss of muscle sensory neurons.
Author(s) -
Lino Tessarollo,
Kristine S. Vogel,
Mary Ellen Palko,
Susan Reid,
Luis F. Parada
Publication year - 1994
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.91.25.11844
Subject(s) - biology , tropomyosin receptor kinase c , neurotrophin 3 , neurotrophin , mutant , low affinity nerve growth factor receptor , tropomyosin receptor kinase b , microbiology and biotechnology , gene targeting , tropomyosin receptor kinase a , receptor tyrosine kinase , nerve growth factor , neurotrophic factors , genetics , receptor , brain derived neurotrophic factor , gene , growth factor , platelet derived growth factor receptor
Neurotrophin 3 (NT-3) is one of four related polypeptide growth factors that share structural and functional homology to nerve growth factor (NGF). NT-3 and its receptor, called neurotrophic tyrosine kinase receptor type 3 (Ntrk3; also called TrkC), are expressed early and throughout embryogenesis. We have inactivated the NT-3 gene in embryonic stem (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 NT-3-deficient mutants fail to thrive and exhibit severe neurological dysfunction. Analysis of mutant embryos uncovers loss of Ntrk3/TrkC-expressing sensory neurons and abnormalities at early stages of sensory neuronal development. NT-3-deficient mice will permit further study of the role of this neurotrophin in neural development.