Continuous and periodic expansion of CAG repeats in Huntington's disease R6/1 mice.

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Continuous and periodic expansion of CAG repeats in Huntington's disease R6/1 mice.
Møllersen, Linda; Rowe, Alexander D; Larsen, Elisabeth; Rognes, Torbjørn; Klungland, Arne
PLoS genetics 2010, 6 (12):e1001242

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dc.contributor.authorMøllersen, Lindaen
dc.contributor.authorRowe, Alexander Den
dc.contributor.authorLarsen, Elisabethen
dc.contributor.authorRognes, Torbjørnen
dc.contributor.authorKlungland, Arneen
dc.identifier.citationPLoS genetics 2010, 6 (12):e1001242en
dc.description.abstractHuntington's disease (HD) is one of several neurodegenerative disorders caused by expansion of CAG repeats in a coding gene. Somatic CAG expansion rates in HD vary between organs, and the greatest instability is observed in the brain, correlating with neuropathology. The fundamental mechanisms of somatic CAG repeat instability are poorly understood, but locally formed secondary DNA structures generated during replication and/or repair are believed to underlie triplet repeat expansion. Recent studies in HD mice have demonstrated that mismatch repair (MMR) and base excision repair (BER) proteins are expansion inducing components in brain tissues. This study was designed to simultaneously investigate the rates and modes of expansion in different tissues of HD R6/1 mice in order to further understand the expansion mechanisms in vivo. We demonstrate continuous small expansions in most somatic tissues (exemplified by tail), which bear the signature of many short, probably single-repeat expansions and contractions occurring over time. In contrast, striatum and cortex display a dramatic--and apparently irreversible--periodic expansion. Expansion profiles displaying this kind of periodicity in the expansion process have not previously been reported. These in vivo findings imply that mechanistically distinct expansion processes occur in different tissues.en
dc.publisherPLoS Geneticsen
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Nevrologi: 752en
dc.titleContinuous and periodic expansion of CAG repeats in Huntington's disease R6/1 mice.en
dc.typeJournal articleen
dc.typepeer revieweden
dc.contributor.departmentCentre for Molecular Biology and Neuroscience, Institute of Medical Microbiology, Oslo University Hospital, Oslo, Norway.en
dc.identifier.journalPLoS geneticsen
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