TY  - JOUR
AU  - Hokkanen, Suvi
AU  - Feldmann, Heidi M
AU  - Ding, Haiyan
AU  - Jung, Christian K E
AU  - Bojarski, Lukasz
AU  - Renner-Müller, Ingrid
AU  - Schüller, Ulrich
AU  - Kretzschmar, Hans
AU  - Wolf, Eckhard
AU  - Herms, Jochen
TI  - Lack of Pur-alpha alters postnatal brain development and causes megalencephaly.
JO  - Human molecular genetics
VL  - 21
IS  - 3
SN  - 0964-6906
CY  - Oxford
PB  - Oxford Univ. Press
M1  - DZNE-2020-02736
SP  - 473-484
PY  - 2012
AB  - 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.
KW  - Animals
KW  - Axons: metabolism
KW  - Brain: growth & development
KW  - Brain: pathology
KW  - Brain Chemistry
KW  - Cell Proliferation
KW  - Cerebellum: cytology
KW  - Cerebellum: growth & development
KW  - Cerebellum: pathology
KW  - Cerebrum: growth & development
KW  - Cerebrum: pathology
KW  - DNA-Binding Proteins: genetics
KW  - DNA-Binding Proteins: physiology
KW  - Hippocampus: cytology
KW  - Hippocampus: growth & development
KW  - Hypertrophy
KW  - Mice
KW  - Mice, Knockout
KW  - Microtubule-Associated Proteins: analysis
KW  - Nerve Tissue Proteins: genetics
KW  - Nerve Tissue Proteins: physiology
KW  - Neurofilament Proteins: metabolism
KW  - Phosphorylation
KW  - DNA-Binding Proteins (NLM Chemicals)
KW  - Microtubule-Associated Proteins (NLM Chemicals)
KW  - Nerve Tissue Proteins (NLM Chemicals)
KW  - Neurofilament Proteins (NLM Chemicals)
KW  - Pura protein, mouse (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:22010047
DO  - DOI:10.1093/hmg/ddr476
UR  - https://pub.dzne.de/record/136414
ER  -