title: FTDP-17 mutations N279K and S305N in tau produce increased splicing of exon 10.
abstract: Missense mutations and intronic mutations in the tau gene cause frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17). Known missense mutations reduce the ability of tau to promote microtubule assembly. Intronic mutations lead to increased mRNA splicing of the alternatively spliced exon 10, resulting in an overproduction of tau isoforms with four microtubule-binding repeats. We show here that the recently identified FTDP-17 missense mutations N279K and S305N do not reduce the ability of tau to promote microtubule assembly. Instead they lead to increased splicing of exon 10, like the intronic mutations. The N279K and S305N mutations define a class of missense mutations in tau whose primary effects are at the RNA level.
authors.affiliation: Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.
authors.forename: M
authors.initials: M
authors.lastname: Hasegawa
authors.forename: M J
authors.initials: MJ
authors.lastname: Smith
authors.forename: M
authors.initials: M
authors.lastname: Iijima
authors.forename: T
authors.initials: T
authors.lastname: Tabira
authors.forename: M
authors.initials: M
authors.lastname: Goedert
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D004247:DNA; D005091:Exons; D006801:Humans; D007438:Introns / Q000235:genetics; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D016297:Mutagenesis, Site-Directed; D020125:Mutation, Missense; D011994:Recombinant Proteins / Q000235:genetics; D016875:tau Proteins / Q000235:genetics*