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Adeno-associated vi...
Adeno-associated viral vector serotypes 1 and 5 targeted to the neonatal rat and pig striatum induce widespread transgene expression in the forebrain
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Kornum, Birgitte R. (author)
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- Stott, Simon (author)
- Lund University,Lunds universitet,Brain Repair and Imaging in Neural Systems (BRAINS),Forskargrupper vid Lunds universitet,Lund University Research Groups
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- Mattsson, Bengt (author)
- Lund University,Lunds universitet,Brain Repair and Imaging in Neural Systems (BRAINS),Forskargrupper vid Lunds universitet,Lund University Research Groups
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- Wisman, Liselijn (author)
- Lund University,Lunds universitet,Brain Repair and Imaging in Neural Systems (BRAINS),Forskargrupper vid Lunds universitet,Lund University Research Groups
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Ettrup, Anders (author)
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- Hermening, Stephan (author)
- Lund University,Lunds universitet,Brain Repair and Imaging in Neural Systems (BRAINS),Forskargrupper vid Lunds universitet,Lund University Research Groups
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Knudsen, Gitte M. (author)
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- Kirik, Deniz (author)
- Lund University,Lunds universitet,Brain Repair and Imaging in Neural Systems (BRAINS),Forskargrupper vid Lunds universitet,Lund University Research Groups
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(creator_code:org_t)
- Elsevier BV, 2010
- 2010
- English.
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In: Experimental Neurology. - : Elsevier BV. - 0014-4886. ; 222:1, s. 70-85
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Abstract
Subject headings
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- Viral vector-mediated gene transfer has emerged as a powerful means to target transgene expression in the central nervous system. Here we characterized the efficacy of serotypes 1 and 5 recombinant adeno-associated virus (rAAV) vectors encoding green fluorescent protein (GFP) after stereotaxic delivery to the neonatal rat and minipig striatum. The efficiency of GFP expression and the phenotype of GFP-positive cells were assessed within the forebrain at different time points up to 12 months after surgery. Both rAAV1-GFP and rAAV5-GFP delivery resulted in transduction of the striatum as well as striatal input and output areas, including large parts of the cortex. In both species, rAAV5 resulted in a more widespread transgene expression compared to rAAV1. In neonatal rats, rAAV5 also transduced several other areas such as the olfactory bulbs, hippocampus, and septum. Phenotypic analysis of the GFP-positive cells, performed using immunohistochemistry and confocal microscopy, showed that most of the GFP-positive cells by either serotype were NeuN-positive neuronal profiles. The rAAV5 vector further displayed the ability to transduce non-neuronal cell types in both rats and pigs, albeit at a low frequency. Our results show that striatal delivery of rAAV5 vectors in the neonatal brain represents a useful tool to express genes of interest both in the basal ganglia and the neocortex. Furthermore, we apply, for the first time, viral vector-mediated gene transfer to the pig brain providing the opportunity to study effects of genetic manipulation in this non-primate large animal species. Finally, we generated an atlas of the Gottingen minipig brain for guiding future studies in this large animal species. (C) 2009 Elsevier Inc. All rights reserved.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
Keyword
- Pig
- Rat
- Neonate
- Cortex
- Striatum
- In vivo gene transfer
- Adeno-associated viral vectors
- Swine
- Stereology
- Confocal microscopy
Publication and Content Type
- art (subject category)
- ref (subject category)
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