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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
16
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pubmed:dateCreated |
1997-2-21
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pubmed:abstractText |
A 9.0-kb fragment of the tyrosine hydroxylase (TH) promoter, previously shown to direct tissue-specific expression in transgenic mice, was fused to an Escherichia coli LacZ reporter gene in a defective herpes simplex virus type-1 (HSV-1) amplicon vector (THlac). The HSV immediate early (IE) 4/5 promoter (HSVlac) was used as a control. LacZ gene expression was visualized by X-Gal histochemical and TH immunocytochemical analysis. Two days and 10 weeks after THlac injection into rat caudate nucleus (CN), X-Gal-stained cells were observed in the substantia nigra (SN) and locus ceruleus (LC) ipsilateral to the injection site. These blue cells were TH-positive neurons as evidenced by double labeling with immunocytochemistry. Moreover, the number of X-Gal+, TH+ (double-positive) neurons in the SN increased at 10 weeks as compared to that seen 2 days after THlac injection. In marked contrast, few double-positive nigral neurons were observed either 2 days or 10 weeks after direct injection of THlac into SN. However, neither nigral nor striatal injection of HSVlac resulted in prolonged gene expression. These results suggest that a neuronal, but not a viral, promoter in an HSV vector can produce cell-type-specific, prolonged, and stable gene expression following retrograde transport. In addition, THlac produced infrequent gene expression in TH-negative cells (CN and dorsal to SN) after THlac injection into CN and SN, respectively. Overall, these results suggest that in some in vivo contexts cell-type-preferred expression can be achieved by a cellular promoter in an amplicon vector. Moreover, they underscore the need for the careful and systematic study of neuronal promoters in HSV vectors.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1043-0342
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
20
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pubmed:volume |
7
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2015-24
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:8930662-Defective Viruses,
pubmed-meshheading:8930662-Gene Expression,
pubmed-meshheading:8930662-Genetic Vectors,
pubmed-meshheading:8930662-Herpesvirus 1, Human,
pubmed-meshheading:8930662-Humans,
pubmed-meshheading:8930662-Injections,
pubmed-meshheading:8930662-Promoter Regions, Genetic,
pubmed-meshheading:8930662-Time Factors,
pubmed-meshheading:8930662-Tyrosine 3-Monooxygenase,
pubmed-meshheading:8930662-beta-Galactosidase
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pubmed:year |
1996
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pubmed:articleTitle |
Prolonged in vivo gene expression driven by a tyrosine hydroxylase promoter in a defective herpes simplex virus amplicon vector.
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pubmed:affiliation |
Laboratory of Molecular Neurobiology, Cornell University Medical College, Burke Research Medical Institute, White Plains, NY 10605, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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