title: Effects on splicing and protein function of three mutations in codon N296 of tau in vitro.
abstract: Three Mutations were recently reported in the same codon (N296) in exon 10 of the tau gene. Two of these mutations, N296N and N296H, lead to a clinical syndrome similar to autosomal dominant fronto-temporal dementia with Parkinsonism linked to chromosome 17. In contrast the third mutation, delN296, gives rise to atypical progressive supranuclear palsy in individuals homozygous for the mutation, but in heterozygous individuals this mutation is incompletely penetrant and associated with a phenotype similar to idiopathic Parkinson's disease. Functional assays were employed to determine the effects of these mutations on alternative splicing of exon 10, on microtubule assembly and self-aggregation of recombinant tau protein. We demonstrate that these mutations exhibit a spectrum of potentially pathogenic changes in tau function, and provide insight into the possible cause of the incompletely penetrant phenotype of the delN296 mutation.
authors.affiliation: Laboratory of Neurogenetics, Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Grover
authors.forename: Michael
authors.initials: M
authors.lastname: DeTure
authors.forename: Shu Hui
authors.initials: SH
authors.lastname: Yen
authors.forename: Mike
authors.initials: M
authors.lastname: Hutton
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D003062:Codon / Q000235:genetics*; D003704:Dementia / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009154:Mutation; D010300:Parkinson Disease / Q000150:complications / Q000235:genetics / Q000378:metabolism; D024801:Tauopathies / Q000209:etiology / Q000235:genetics; D016875:tau Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D003062:Codon; D016875:tau Proteins