title: Altered microtubule organization in small-calibre axons of mice lacking tau protein.
abstract: The tau gene encodes a protein (Tau) that is a major neuronal microtubule-associated protein localized mostly in axons. It has microtubule-binding and tubulin-polymerizing activity in vitro and is thought to make short crossbridges between axonal microtubules. Further, tau-transfected non-neuronal cells extend long axon-like processes in which microtubule bundles resembling those in axons are formed. In contrast, tau antisense oligonucleotides selectively suppress axonal elongation in cultured neurons. Thus tau is thought to be essential for neuronal cell morphogenesis, especially axonal elongation and maintenance. To test this hypothesis, we used gene targeting to produce mice lacking the tau gene. We show that the nervous system of tau-deficient mice appears to be normal immunohistologically. Furthermore, axonal elongation is not affected in cultured neurons. But in some small-calibre axons, microtubule stability is decreased and microtubule organization is significantly changed. We observed an increase in microtubule-associated protein 1A which may compensate for the functions of tau in large-calibre axons. Our results argue against the suggested role of tau in axonal elongation but confirm that it is crucial in the stabilization and organization of axonal microtubules in a certain type of axon.
authors.affiliation: Department of Anatomy and Cell Biology, School of Medicine, University of Tokyo, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Harada
authors.forename: K
authors.initials: K
authors.lastname: Oguchi
authors.forename: S
authors.initials: S
authors.lastname: Okabe
authors.forename: J
authors.initials: J
authors.lastname: Kuno
authors.forename: S
authors.initials: S
authors.lastname: Terada
authors.forename: T
authors.initials: T
authors.lastname: Ohshima
authors.forename: R
authors.initials: R
authors.lastname: Sato-Yoshitake
authors.forename: Y
authors.initials: Y
authors.lastname: Takei
authors.forename: T
authors.initials: T
authors.lastname: Noda
authors.forename: N
authors.initials: N
authors.lastname: Hirokawa
mesh_terms: D000818:Animals; D001369:Axons / Q000648:ultrastructure*; D002460:Cell Line; D003001:Cloning, Molecular; D005260:Female; D006624:Hippocampus / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008870:Microtubules / Q000648:ultrastructure*; D009024:Morphogenesis / Q000502:physiology; D009154:Mutation; D009474:Neurons / Q000502:physiology / Q000648:ultrastructure; D016875:tau Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology
chemical_list: D016875:tau Proteins