Viral Vector-Based Dissection of Marmoset GFAP Promoter in Mouse and Marmoset Brains
Adeno-associated virus (AAV) vectors are small in diameter, diffuse easily in the brain, and represent a highly efficient means by which to transfer a transgene to the brain of a large animal. A major demerit of AAV vectors is their limited accommodation capacity for transgenes. Thus, a compact prom...
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| creator | Shinohara, Yoichiro Konno, Ayumu Takahashi, Nobutaka Matsuzaki, Yasunori Kishi, Shoji Hirai, Hirokazu |
| description | Adeno-associated virus (AAV) vectors are small in diameter, diffuse easily in the brain, and represent a highly efficient means by which to transfer a transgene to the brain of a large animal. A major demerit of AAV vectors is their limited accommodation capacity for transgenes. Thus, a compact promoter is useful when delivering large transgenes via AAV vectors. In the present study, we aimed to identify the shortest astrocyte-specific GFAP promoter region that could be used for AAV-vector-mediated transgene expression in the marmoset brain. The 2.0-kb promoter region upstream of the GFAP gene was cloned from the marmoset genome, and short promoters (1.6 kb, 1.4 kb, 0.6 kb, 0.3 kb and 0.2 kb) were obtained by progressively deleting the original 2.0-kb promoter from the 5' end. The short promoters were screened in the mouse cerebellum in terms of their strength and astrocyte specificity. We found that the 0.3-kb promoter maintained 40% of the strength of the original 2.0-kb promoter, and approximately 90% of its astrocyte specificity. These properties were superior to those of the 1.4-kb, 0.6-kb (20% promoter strength) and 0.2-kb (70% astrocyte specificity) promoters. Then, we verified whether the 0.3-kb GFAP promoter retained astrocyte specificity in the marmoset cerebral cortex. Injection of viral vectors carrying the 0.3-kb marmoset GFAP promoter specifically transduced astrocytes in both the cerebral cortex and cerebellar cortex of the marmoset. These results suggest that the compact 0.3-kb promoter region serves as an astrocyte-specific promoter in the marmoset brain, which permits us to express a large gene by AAV vectors that have a limited accommodation capacity. |
| doi_str_mv | 10.1371/journal.pone.0162023 |
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A major demerit of AAV vectors is their limited accommodation capacity for transgenes. Thus, a compact promoter is useful when delivering large transgenes via AAV vectors. In the present study, we aimed to identify the shortest astrocyte-specific GFAP promoter region that could be used for AAV-vector-mediated transgene expression in the marmoset brain. The 2.0-kb promoter region upstream of the GFAP gene was cloned from the marmoset genome, and short promoters (1.6 kb, 1.4 kb, 0.6 kb, 0.3 kb and 0.2 kb) were obtained by progressively deleting the original 2.0-kb promoter from the 5' end. The short promoters were screened in the mouse cerebellum in terms of their strength and astrocyte specificity. We found that the 0.3-kb promoter maintained 40% of the strength of the original 2.0-kb promoter, and approximately 90% of its astrocyte specificity. These properties were superior to those of the 1.4-kb, 0.6-kb (20% promoter strength) and 0.2-kb (70% astrocyte specificity) promoters. Then, we verified whether the 0.3-kb GFAP promoter retained astrocyte specificity in the marmoset cerebral cortex. Injection of viral vectors carrying the 0.3-kb marmoset GFAP promoter specifically transduced astrocytes in both the cerebral cortex and cerebellar cortex of the marmoset. These results suggest that the compact 0.3-kb promoter region serves as an astrocyte-specific promoter in the marmoset brain, which permits us to express a large gene by AAV vectors that have a limited accommodation capacity.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0162023</identifier><identifier>PMID: 27571575</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Accommodation ; Adeno-associated virus ; Animals ; Astrocytes ; Biology and Life Sciences ; Brain ; Brain - metabolism ; Brain research ; Callithrix ; Callithrix jacchus ; Cerebellum ; Cerebellum - metabolism ; Cerebral cortex ; Gene expression ; Genetic vectors ; Genetic Vectors - genetics ; Genomes ; Glial fibrillary acidic protein ; Glial Fibrillary Acidic Protein - genetics ; HEK293 Cells ; Hepatitis ; Humans ; Immunohistochemistry ; Laboratory animals ; Lentivirus - genetics ; Medicine ; Medicine and Health Sciences ; Mice ; Mice, Inbred C57BL ; Neurosciences ; Physiological aspects ; Polymerase chain reaction ; Promoter Regions, Genetic - genetics ; Promoters ; Promoters (Genetics) ; Research and Analysis Methods ; Rodents ; Transgenes ; University graduates ; Virology ; Viruses</subject><ispartof>PloS one, 2016-08, Vol.11 (8), p.e0162023-e0162023</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Shinohara et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2016 Shinohara et al 2016 Shinohara et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c791t-188b09382646fa4bf6b2edcf562b06fe7b7a721142e9690f6e124e09e26e80ab3</citedby><cites>FETCH-LOGICAL-c791t-188b09382646fa4bf6b2edcf562b06fe7b7a721142e9690f6e124e09e26e80ab3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5003399/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5003399/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27571575$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Nagai, Yoshitaka</contributor><creatorcontrib>Shinohara, Yoichiro</creatorcontrib><creatorcontrib>Konno, Ayumu</creatorcontrib><creatorcontrib>Takahashi, Nobutaka</creatorcontrib><creatorcontrib>Matsuzaki, Yasunori</creatorcontrib><creatorcontrib>Kishi, Shoji</creatorcontrib><creatorcontrib>Hirai, Hirokazu</creatorcontrib><title>Viral Vector-Based Dissection of Marmoset GFAP Promoter in Mouse and Marmoset Brains</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Adeno-associated virus (AAV) vectors are small in diameter, diffuse easily in the brain, and represent a highly efficient means by which to transfer a transgene to the brain of a large animal. 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A major demerit of AAV vectors is their limited accommodation capacity for transgenes. Thus, a compact promoter is useful when delivering large transgenes via AAV vectors. In the present study, we aimed to identify the shortest astrocyte-specific GFAP promoter region that could be used for AAV-vector-mediated transgene expression in the marmoset brain. The 2.0-kb promoter region upstream of the GFAP gene was cloned from the marmoset genome, and short promoters (1.6 kb, 1.4 kb, 0.6 kb, 0.3 kb and 0.2 kb) were obtained by progressively deleting the original 2.0-kb promoter from the 5' end. The short promoters were screened in the mouse cerebellum in terms of their strength and astrocyte specificity. We found that the 0.3-kb promoter maintained 40% of the strength of the original 2.0-kb promoter, and approximately 90% of its astrocyte specificity. These properties were superior to those of the 1.4-kb, 0.6-kb (20% promoter strength) and 0.2-kb (70% astrocyte specificity) promoters. Then, we verified whether the 0.3-kb GFAP promoter retained astrocyte specificity in the marmoset cerebral cortex. Injection of viral vectors carrying the 0.3-kb marmoset GFAP promoter specifically transduced astrocytes in both the cerebral cortex and cerebellar cortex of the marmoset. These results suggest that the compact 0.3-kb promoter region serves as an astrocyte-specific promoter in the marmoset brain, which permits us to express a large gene by AAV vectors that have a limited accommodation capacity.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27571575</pmid><doi>10.1371/journal.pone.0162023</doi><tpages>e0162023</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Accommodation Adeno-associated virus Animals Astrocytes Biology and Life Sciences Brain Brain - metabolism Brain research Callithrix Callithrix jacchus Cerebellum Cerebellum - metabolism Cerebral cortex Gene expression Genetic vectors Genetic Vectors - genetics Genomes Glial fibrillary acidic protein Glial Fibrillary Acidic Protein - genetics HEK293 Cells Hepatitis Humans Immunohistochemistry Laboratory animals Lentivirus - genetics Medicine Medicine and Health Sciences Mice Mice, Inbred C57BL Neurosciences Physiological aspects Polymerase chain reaction Promoter Regions, Genetic - genetics Promoters Promoters (Genetics) Research and Analysis Methods Rodents Transgenes University graduates Virology Viruses |
| title | Viral Vector-Based Dissection of Marmoset GFAP Promoter in Mouse and Marmoset Brains |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-31T12%3A08%3A10IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Viral%20Vector-Based%20Dissection%20of%20Marmoset%20GFAP%20Promoter%20in%20Mouse%20and%20Marmoset%20Brains&rft.jtitle=PloS%20one&rft.au=Shinohara,%20Yoichiro&rft.date=2016-08-29&rft.volume=11&rft.issue=8&rft.spage=e0162023&rft.epage=e0162023&rft.pages=e0162023-e0162023&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0162023&rft_dat=%3Cgale_plos_%3EA461910842%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1814902766&rft_id=info:pmid/27571575&rft_galeid=A461910842&rft_doaj_id=oai_doaj_org_article_1c7bd2a3e0304b63a0d9ab4aa5cd9fc7&rfr_iscdi=true |