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@ARTICLE{Hokkanen:136414,
author = {Hokkanen, Suvi and Feldmann, Heidi M and Ding, Haiyan and
Jung, Christian K E and Bojarski, Lukasz and Renner-Müller,
Ingrid and Schüller, Ulrich and Kretzschmar, Hans and Wolf,
Eckhard and Herms, Jochen},
title = {{L}ack of {P}ur-alpha alters postnatal brain development
and causes megalencephaly.},
journal = {Human molecular genetics},
volume = {21},
number = {3},
issn = {0964-6906},
address = {Oxford},
publisher = {Oxford Univ. Press},
reportid = {DZNE-2020-02736},
pages = {473-484},
year = {2012},
abstract = {Pur-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.},
keywords = {Animals / Axons: metabolism / Brain: growth $\&$
development / Brain: pathology / Brain Chemistry / Cell
Proliferation / Cerebellum: cytology / Cerebellum: growth
$\&$ development / Cerebellum: pathology / Cerebrum: growth
$\&$ development / Cerebrum: pathology / DNA-Binding
Proteins: genetics / DNA-Binding Proteins: physiology /
Hippocampus: cytology / Hippocampus: growth $\&$ development
/ Hypertrophy / Mice / Mice, Knockout /
Microtubule-Associated Proteins: analysis / Nerve Tissue
Proteins: genetics / Nerve Tissue Proteins: physiology /
Neurofilament Proteins: metabolism / Phosphorylation /
DNA-Binding Proteins (NLM Chemicals) /
Microtubule-Associated Proteins (NLM Chemicals) / Nerve
Tissue Proteins (NLM Chemicals) / Neurofilament Proteins
(NLM Chemicals) / Pura protein, mouse (NLM Chemicals)},
cin = {München Pre 2020 / AG Herms / Ext LMU ZNP},
ddc = {570},
cid = {I:(DE-2719)6000016 / I:(DE-2719)1110001 /
I:(DE-2719)5000051},
pnm = {342 - Disease Mechanisms and Model Systems (POF3-342)},
pid = {G:(DE-HGF)POF3-342},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:22010047},
doi = {10.1093/hmg/ddr476},
url = {https://pub.dzne.de/record/136414},
}