title: Functional effects of tau gene mutations deltaN296 and N296H.
abstract: Mutations in the tau gene cause frontotemporal dementia and parkinsonism linked to chromosome-17 (FTDP-17). Functionally, about half of the known mutations increase the alternative mRNA splicing of exon 10 of the tau gene, resulting in the overproduction of tau isoforms with four microtubule-binding repeats. The other mutations reduce the ability of tau to interact with microtubules, with some mutations also increasing the propensity of tau to assemble into filaments. Here we have examined the functional effects of the recently described tau gene mutations deltaN296 and N296H. Both mutations reduced the ability of tau to promote microtubule assembly, without having a significant effect on tau filament formation. By exon trapping, they increased the splicing of exon 10. DeltaN296 and N296H thus define a class of tau mutations with effects at both the RNA and the protein level.
authors.affiliation: Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Yoshida
authors.forename: R Anthony
authors.initials: RA
authors.lastname: Crowther
authors.forename: Michel
authors.initials: M
authors.lastname: Goedert
mesh_terms: D005091:Exons / Q000235:genetics; D006801:Humans; D008854:Microscopy, Electron; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D016297:Mutagenesis, Site-Directed / Q000502:physiology; D016875:tau Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D016875:tau Proteins