Document Detail


Characterization of the properties of seven promoters in the motor cortex of rats and monkeys after lentiviral vector-mediated gene transfer.
MedLine Citation:
PMID:  23964981     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Lentiviral vectors deliver transgenes efficiently to a wide range of neuronal cell types in the mammalian central nervous system. To drive gene expression, internal promoters are essential; however, the in vivo properties of promoters, such as their cell-type specificity and gene expression activity are not well known, especially in the non-human primate brain. Here, the properties of five ubiquitous (murine stem cell virus (MSCV), cytomegalovirus (CMV), CMV early enhancer/chicken ß actin (CAG), human elongation factor-1 alpha (EF1α), Rous sarcoma virus (RSV)) and two cell-type specific promoters (rat Synapsin I, and mouse alpha-calcium/calmodulin-dependent protein kinase II (CaMKIIα)) in rat and monkey motor cortices in vivo were characterized. Vesicular stomatitis virus-G (VSV-G) pseudotyped lentiviral vectors expressing enhanced green fluorescent protein (EGFP) under the control of the different promoters were prepared and injected into rat and monkey motor cortices. Immunohistochemical analysis revealed that all of the VSV-G pseudotyped lentiviral vectors had strong endogenous neuronal tropisms in rat and monkey brains. Among the seven promoters, the CMV promoter showed modest expression in glial cells (9.4%) of the rat brain, whereas the five ubiquitous promoters (MSCV, CMV, CAG, EF1α, and RSV) showed expression in glial cells (7.0 - 14.7%) in the monkey brain. Cell-type specific Synapsin I and CaMKIIα promoters showed excitatory neuron-specific expression in the monkey brain (Synapsin I, 99.7%; CaMKIIα, 100.0%), but their specificities to excitatory neurons were significantly lower in the rat brain (Synapsin I, 94.6%; CaMKIIα, 93.7%). These findings could be useful in basic and clinical neuroscience research for the design of vectors that efficiently deliver and express transgenes into rat and monkey brains.
Authors:
Masae Yaguchi; Yohei Ohashi; Tadashi Tsubota; Ayana Sato; Kenji W Koyano; Ningqun Wang; Yasushi Miyashita
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-8-21
Journal Detail:
Title:  Human gene therapy methods     Volume:  -     ISSN:  1946-6544     ISO Abbreviation:  Hum Gene Ther Methods     Publication Date:  2013 Aug 
Date Detail:
Created Date:  2013-8-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101573202     Medline TA:  Hum Gene Ther Methods     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
The University of Tokyo School of Medicine, Physiology, Tokyo, Tokyo, Japan ; yaguchi@m.u-tokyo.ac.jp.
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