| Nurr1 is required for maintenance of maturing and adult midbrain dopamine neurons. | |
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MedLine Citation:
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PMID: 20016108 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Transcription factors involved in the specification and differentiation of neurons often continue to be expressed in the adult brain, but remarkably little is known about their late functions. Nurr1, one such transcription factor, is essential for early differentiation of midbrain dopamine (mDA) neurons but continues to be expressed into adulthood. In Parkinson's disease, Nurr1 expression is diminished and mutations in the Nurr1 gene have been identified in rare cases of disease; however, the significance of these observations remains unclear. Here, a mouse strain for conditional targeting of the Nurr1 gene was generated, and Nurr1 was ablated either at late stages of mDA neuron development by crossing with mice carrying Cre under control of the dopamine transporter locus or in the adult brain by transduction of adeno-associated virus Cre-encoding vectors. Nurr1 deficiency in maturing mDA neurons resulted in rapid loss of striatal DA, loss of mDA neuron markers, and neuron degeneration. In contrast, a more slowly progressing loss of striatal DA and mDA neuron markers was observed after ablation in the adult brain. As in Parkinson's disease, neurons of the substantia nigra compacta were more vulnerable than cells in the ventral tegmental area when Nurr1 was ablated at late embryogenesis. The results show that developmental pathways play key roles for the maintenance of terminally differentiated neurons and suggest that disrupted function of Nurr1 and other developmental transcription factors may contribute to neurodegenerative disease. |
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Authors:
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Banafsheh Kadkhodaei; Takehito Ito; Eliza Joodmardi; Bengt Mattsson; Claude Rouillard; Manolo Carta; Shin-ichi Muramatsu; Chiho Sumi-Ichinose; Takahide Nomura; Daniel Metzger; Pierre Chambon; Eva Lindqvist; Nils-Göran Larsson; Lars Olson; Anders Björklund; Hiroshi Ichinose; Thomas Perlmann |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of neuroscience : the official journal of the Society for Neuroscience Volume: 29 ISSN: 1529-2401 ISO Abbreviation: J. Neurosci. Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2009-12-17 Completed Date: 2010-01-26 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8102140 Medline TA: J Neurosci Country: United States |
Other Details:
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Languages: eng Pagination: 15923-32 Citation Subset: IM |
Affiliation:
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Ludwig Institute for Cancer Research, Stockholm Branch, SE-171 77 Stockholm, Sweden. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Age Factors Animals Embryonic Stem Cells / cytology, physiology Female Gene Targeting Integrases / genetics Mesencephalon / cytology*, growth & development*, physiology Mice Mice, Transgenic Neurogenesis / genetics Neurons / cytology*, physiology* Nuclear Receptor Subfamily 4, Group A, Member 2 / deficiency, genetics, physiology* Pregnancy |
| Chemical | |
Reg. No./Substance:
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0/Nuclear Receptor Subfamily 4, Group A, Member 2; EC 2.7.7.-/Cre recombinase; EC 2.7.7.-/Integrases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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