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000136414 0247_ $$2doi$$a10.1093/hmg/ddr476
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000136414 0247_ $$2ISSN$$a1460-2083
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000136414 041__ $$aEnglish
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000136414 1001_ $$0P:(DE-2719)9000134$$aHokkanen, Suvi$$b0$$eFirst author
000136414 245__ $$aLack of Pur-alpha alters postnatal brain development and causes megalencephaly.
000136414 260__ $$aOxford$$bOxford Univ. Press$$c2012
000136414 264_1 $$2Crossref$$3online$$bOxford University Press (OUP)$$c2011-10-18
000136414 264_1 $$2Crossref$$3print$$bOxford University Press (OUP)$$c2012-02-01
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000136414 520__ $$aPur-alpha (Purα) plays an important role in a variety of cellular processes including transcriptional regulation, cell proliferation and oncogenic transformation. To better understand the role of Purα in the developing and mature brain, we generated Purα-deficient mice, which we were able to raise to the age of six months. Purα(-/-) mice were born with no obvious pathological condition. We obtained convincing evidence that lack of Purα prolongs the postnatal proliferation of neuronal precursor cells both in the hippocampus and in the cerebellum, however, without affecting the overall number of postmitotic neurons. Independent of these findings, we observed alterations in the expression and distribution of the dendritic protein MAP2, the translation of which has been proposed previously to be Purα-dependent. At the age of 2 weeks, Purα(-/-) mice generated a continuous tremor which persisted throughout lifetime. Finally, adult Purα(-/-) mice displayed a megalencephaly and histopathological findings including axonal swellings and hyperphosphorylation of neurofilaments. Our studies underline the importance of Purα in the proliferation of neuronal precursor cells during postnatal brain development and suggest a role for Purα in the regulation of the expression and cellular distribution of dendritic and axonal proteins. Since recent studies implicate a link between Purα and the fragile X tremor/ataxia syndrome, our Purα(-/-) mouse model will provide new opportunities for understanding the mechanisms of neurodegeneration.
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000136414 650_7 $$2NLM Chemicals$$aDNA-Binding Proteins
000136414 650_7 $$2NLM Chemicals$$aMicrotubule-Associated Proteins
000136414 650_7 $$2NLM Chemicals$$aNerve Tissue Proteins
000136414 650_7 $$2NLM Chemicals$$aNeurofilament Proteins
000136414 650_7 $$2NLM Chemicals$$aPura protein, mouse
000136414 650_2 $$2MeSH$$aAnimals
000136414 650_2 $$2MeSH$$aAxons: metabolism
000136414 650_2 $$2MeSH$$aBrain: growth & development
000136414 650_2 $$2MeSH$$aBrain: pathology
000136414 650_2 $$2MeSH$$aBrain Chemistry
000136414 650_2 $$2MeSH$$aCell Proliferation
000136414 650_2 $$2MeSH$$aCerebellum: cytology
000136414 650_2 $$2MeSH$$aCerebellum: growth & development
000136414 650_2 $$2MeSH$$aCerebellum: pathology
000136414 650_2 $$2MeSH$$aCerebrum: growth & development
000136414 650_2 $$2MeSH$$aCerebrum: pathology
000136414 650_2 $$2MeSH$$aDNA-Binding Proteins: genetics
000136414 650_2 $$2MeSH$$aDNA-Binding Proteins: physiology
000136414 650_2 $$2MeSH$$aHippocampus: cytology
000136414 650_2 $$2MeSH$$aHippocampus: growth & development
000136414 650_2 $$2MeSH$$aHypertrophy
000136414 650_2 $$2MeSH$$aMice
000136414 650_2 $$2MeSH$$aMice, Knockout
000136414 650_2 $$2MeSH$$aMicrotubule-Associated Proteins: analysis
000136414 650_2 $$2MeSH$$aNerve Tissue Proteins: genetics
000136414 650_2 $$2MeSH$$aNerve Tissue Proteins: physiology
000136414 650_2 $$2MeSH$$aNeurofilament Proteins: metabolism
000136414 650_2 $$2MeSH$$aPhosphorylation
000136414 7001_ $$aFeldmann, Heidi M$$b1
000136414 7001_ $$aDing, Haiyan$$b2
000136414 7001_ $$0P:(DE-2719)9000145$$aJung, Christian K E$$b3
000136414 7001_ $$aBojarski, Lukasz$$b4
000136414 7001_ $$aRenner-Müller, Ingrid$$b5
000136414 7001_ $$0P:(DE-2719)9000979$$aSchüller, Ulrich$$b6$$udzne
000136414 7001_ $$0P:(DE-2719)9000168$$aKretzschmar, Hans$$b7
000136414 7001_ $$aWolf, Eckhard$$b8
000136414 7001_ $$0P:(DE-2719)2810441$$aHerms, Jochen$$b9$$eLast author
000136414 77318 $$2Crossref$$3journal-article$$a10.1093/hmg/ddr476$$b : Oxford University Press (OUP), 2011-10-18$$n3$$p473-484$$tHuman Molecular Genetics$$v21$$x0964-6906$$y2011
000136414 773__ $$0PERI:(DE-600)1474816-2$$a10.1093/hmg/ddr476$$gVol. 21, no. 3, p. 473 - 484$$n3$$p473-484$$q21:3<473 - 484$$tHuman molecular genetics$$v21$$x0964-6906$$y2011
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