机构：[1]Department of Physiology, The University of Tokyo School of Medicine, Tokyo 113-0033, Japan.[2]Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Saitama, Japan.[3]Department of Physics, The University of Tokyo School of Science, Tokyo 113-0033, Japan.[4]Department of Traditional Chinese Medicine, Xuanwu Hospital of Capital Medical University, Beijing 100053, China.首都医科大学宣武医院
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 nonhuman primate brain. Here, the properties of five ubiquitous promoters (murine stem cell virus [MSCV], cytomegalovirus [CMV], CMV early enhancer/chicken beta-actin [CAG], human elongation factor-1 alpha [EF-1 alpha], and Rous sarcoma virus [RSV]) and two cell type-specific promoters (rat synapsin I and mouse alpha-calcium/calmodulin-dependent protein kinase II [CaMKII alpha]) 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 various 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, EF-1 alpha, and RSV) showed expression in glial cells (7.0-14.7%) in the monkey brain. Cell type-specific synapsin I and CaMKII alpha promoters showed excitatory neuron-specific expression in the monkey brain (synapsin I, 99.7%; CaMKII alpha, 100.0%), but their specificities for excitatory neurons were significantly lower in the rat brain (synapsin I, 94.6%; CaMKII alpha, 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.
基金：
Grant-in-Aid for Specially Promoted Research from the Ministry for Education,Culture, Sports, Science, and Technology (MEXT)(19002010)
a Grant-in-Aid for Scientific Research(24220008)
the Global COE Program (Integrative Life Science Based on the Study of Biosignaling Mechanisms)
the Japan Science and Technology Agency
a Grant-in-Aid for Young Scientists from MEXT (23700489)
Uehara Memorial Fund
the Japan Society for the Promotion of Science ( JSPS) Research Fellowships (206956 and 235569)
语种：
外文
被引次数：
WOS：
PubmedID：
第一作者：
第一作者机构：[1]Department of Physiology, The University of Tokyo School of Medicine, Tokyo 113-0033, Japan.[2]Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Saitama, Japan.
共同第一作者：
通讯作者：
通讯机构：[*1]Department of Physiology The University of Tokyo School of Medicine 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 Japan
推荐引用方式(GB/T 7714)：
Masae Yaguchi,Yohei Ohashi,Tadashi Tsubota,et al.Characterization of the Properties of Seven Promoters in the Motor Cortex of Rats and Monkeys After Lentiviral Vector-Mediated Gene Transfer[J].HUMAN GENE THERAPY METHODS.2013,24(6):333-344.doi:10.1089/hgtb.2012.238.
APA：
Masae Yaguchi,Yohei Ohashi,Tadashi Tsubota,Ayana Sato,Kenji W. Koyano...&Yasushi Miyashita.(2013).Characterization of the Properties of Seven Promoters in the Motor Cortex of Rats and Monkeys After Lentiviral Vector-Mediated Gene Transfer.HUMAN GENE THERAPY METHODS,24,(6)
MLA：
Masae Yaguchi,et al."Characterization of the Properties of Seven Promoters in the Motor Cortex of Rats and Monkeys After Lentiviral Vector-Mediated Gene Transfer".HUMAN GENE THERAPY METHODS 24..6(2013):333-344
