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UBB<jats:sup>+1<\/jats:sup>, a mutant ubiquitin, is one of the proteins accumulating in the neuropathological hallmarks of tauopathies, including Alzheimer's disease, and polyglutamine diseases. In vitro, UBB<jats:sup>+1<\/jats:sup> properties shift from a proteasomal ubiquitin\u2010fusion degradation substrate at low expression levels to a proteasome inhibitor at high expression levels. Here we report on a novel transgenic mouse line (line 6663) expressing low levels of neuronal UBB<jats:sup>+1<\/jats:sup>. In these mice, UBB<jats:sup>+1<\/jats:sup> protein is scarcely detectable in the neuronal cell population. Accumulation of UBB<jats:sup>+1<\/jats:sup> commences only after intracranial infusion of the proteasome inhibitors lactacystin or MG262, showing that, at these low expression levels, the UBB<jats:sup>+1<\/jats:sup> protein is a substrate for proteasomal degradation in vivo. In addition, accumulation of the protein serves as a reporter for proteasome inhibition. These findings strengthen our proposition that, in healthy brain, UBB<jats:sup>+1<\/jats:sup> is continuously degraded and disease\u2010related UBB<jats:sup>+1<\/jats:sup> accumulation serves as an endogenous marker for proteasomal dysfunction. This novel transgenic line can give more insight into the intrinsic properties of UBB<jats:sup>+1<\/jats:sup> and its role in neurodegenerative disease. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.22396","type":"journal-article","created":{"date-parts":[[2010,3,25]],"date-time":"2010-03-25T04:27:27Z","timestamp":1269491247000},"page":"2325-2337","source":"Crossref","is-referenced-by-count":14,"title":["Low levels of mutant ubiquitin are degraded by the proteasome in vivo"],"prefix":"10.1002","volume":"88","author":[{"given":"Paula","family":"van Tijn","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marian C.","family":"Verhage","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Hobo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fred W.","family":"van 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