Source:http://linkedlifedata.com/resource/pubmed/id/12356765
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rdf:type | |
lifeskim:mentions | |
pubmed:dateCreated |
2002-11-26
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pubmed:abstractText |
The postnatal appearance and up-regulation of the NR2A subunit of the N-methyl-d-aspartate receptor contributes to the functional heterogeneity of the receptor during development. To elucidate the molecular mechanisms that regulate the neural and developmental specific expression of NR2A, an upstream approximately 9-kb region of the gene harboring the promoter was isolated and characterized in transgenic mice and transfected cortical neurons. Transgenic mouse lines generated with luciferase reporter constructs driven by either 9 or 1 kb of upstream sequence selectively transcribe the transgene in brain, as compared with other non-neural tissues. Reporter luciferase levels in dissociated cultures made from these mice are over 100-fold greater in neuronal/glial co-cultures than in pure glial cultures. Analysis of NR2A 5'-nested deletions in transfected cultures of cortical neurons and glia indicate that while sequences residing upstream of -1079 bp augment NR2A neuronal expression, sequences between -486 and -447 bp are sufficient to maintain neuronal preference. An RE1/NRSE element is not necessary for NR2A neuron specificity. Furthermore, comparison of the 5'-deletion constructs in cortical neurons grown for 5, 8, 11, or 14 days in vitro indicate that sequences between -1253 and -1180 bp are necessary for maturational up-regulation of NR2A. Thus, different cis-acting sequences control the regional and temporal expression of NR2A, implicating distinct regulatory pathways.
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pubmed:language |
eng
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pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:author | |
pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
46374-84
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pubmed:dateRevised |
2006-10-27
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pubmed:articleTitle |
Analysis of transcriptional regulatory sequences of the N-methyl-D-aspartate receptor 2A subunit gene in cultured cortical neurons and transgenic mice.
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pubmed:affiliation |
Section of Molecular Neurobiology, NICHD, National Institutes of Health, Bethesda, Maryland 20892-4480, USA.
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