Mutations in MAPT give rise to aneuploidy in animal models of tauopathy
| Autor: | Donatella Conconi, Michela Mangieri, Laura Paoletta, Leda Dalprà, Fabrizio Tagliavini, Elena Panzeri, Maria Giulia Ferretti, Giacomina Rossi, Margherita Ruggerone, Elena Piccoli |
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| Přispěvatelé: | Rossi, G, Conconi, D, Panzeri, E, Paoletta, L, Piccoli, E, Ferretti, M, Mangieri, M, Ruggerone, M, Dalpra', L, Tagliavini, F |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
Tau protein Gene Dosage Aneuploidy Mice Transgenic tau Proteins Biology medicine.disease_cause Cellular and Molecular Neuroscience Cytogenetics Mice Chromosome instability Genetics medicine MAPT Animals Humans Genetics(clinical) Lymphocytes Genetics (clinical) Hemizygote Mutation Genome Neurodegeneration Homozygote Chromosome Mapping Karyotype medicine.disease Animal models Tauopathy Disease Models Animal Gene Expression Regulation Tauopathies Karyotyping biology.protein Original Article Tau Tau MAPT Mutation Tauopathy Animal models Cytogenetics Aneuploidy Spleen |
| Zdroj: | Neurogenetics |
| ISSN: | 1364-6753 1364-6745 |
| Popis: | Tau is a major microtubule-associated protein in brain neurons. Its misfolding and accumulation cause neurodegenerative diseases characterized by brain atrophy and dementia, named tauopathies. Genetic forms are caused by mutations of microtubule-associated protein tau gene (MAPT). Tau is expressed also in nonneural tissues such as lymphocytes. Tau has been recently recognized as a multifunctional protein, and in particular, some findings supported a role in genome stability. In fact, peripheral cells of patients affected by frontotemporal dementia carrying different MAPT mutations showed structural and numerical chromosome aberrations. The aim of this study was to assess chromosome stability in peripheral cell from two animal models of genetic tauopathy, JNPL3 and PS19 mouse strains expressing the human tau carrying the P301L and P301S mutations, respectively, to confirm the previous data on humans. After demonstrating the presence of mutated tau in spleen, we performed standard cytogenetic analysis of splenic lymphocytes from homozygous and hemizygous JNPL3, hemizygous PS19, and relevant controls. Losses and gains of chromosomes (aneuploidy) were evaluated. We detected a significantly higher level of aneuploidy in JNPL3 and PS19 than in control mice. Moreover, in JNPL3, the aneuploidy was higher in homozygotes than in hemizygotes, demonstrating a gene dose effect, which appeared also to be age independent. Our results show that mutated tau is associated with chromosome instability. It is conceivable to hypothesize that in genetic tauopathies the aneuploidy may be present also in central nervous system, possibly contributing to neurodegeneration. |
| Databáze: | OpenAIRE |
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