PMID- 27571575
OWN - NLM
STAT- MEDLINE
DCOM- 20170818
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 11
IP  - 8
DP  - 2016
TI  - Viral Vector-Based Dissection of Marmoset GFAP Promoter in Mouse and Marmoset 
      Brains.
PG  - e0162023
LID - 10.1371/journal.pone.0162023 [doi]
LID - e0162023
AB  - 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.
FAU - Shinohara, Yoichiro
AU  - Shinohara Y
AD  - Department of Neurophysiology & Neural Repair, Gunma University Graduate School 
      of Medicine, Maebashi, Gunma, Japan.
AD  - Department of Ophthalmology, Gunma University Graduate School of Medicine, 
      Maebashi, Gunma, Japan.
FAU - Konno, Ayumu
AU  - Konno A
AD  - Department of Neurophysiology & Neural Repair, Gunma University Graduate School 
      of Medicine, Maebashi, Gunma, Japan.
FAU - Takahashi, Nobutaka
AU  - Takahashi N
AD  - Department of Neurophysiology & Neural Repair, Gunma University Graduate School 
      of Medicine, Maebashi, Gunma, Japan.
FAU - Matsuzaki, Yasunori
AU  - Matsuzaki Y
AD  - Department of Neurophysiology & Neural Repair, Gunma University Graduate School 
      of Medicine, Maebashi, Gunma, Japan.
FAU - Kishi, Shoji
AU  - Kishi S
AD  - Department of Ophthalmology, Gunma University Graduate School of Medicine, 
      Maebashi, Gunma, Japan.
FAU - Hirai, Hirokazu
AU  - Hirai H
AD  - Department of Neurophysiology & Neural Repair, Gunma University Graduate School 
      of Medicine, Maebashi, Gunma, Japan.
AD  - Research Program for Neural Signalling, Division of Endocrinology, Metabolism and 
      Signal Research, Gunma University Initiative for Advanced Research, Maebashi, 
      Gunma, Japan.
LA  - eng
PT  - Journal Article
DEP - 20160829
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Glial Fibrillary Acidic Protein)
SB  - IM
MH  - Animals
MH  - Brain/*metabolism
MH  - Callithrix
MH  - Cerebellum/metabolism
MH  - Genetic Vectors/genetics
MH  - Glial Fibrillary Acidic Protein/*genetics
MH  - HEK293 Cells
MH  - Humans
MH  - Immunohistochemistry
MH  - Lentivirus/genetics
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Promoter Regions, Genetic/*genetics
PMC - PMC5003399
COIS- The authors have declared that no competing interests exist.
EDAT- 2016/08/30 06:00
MHDA- 2017/08/19 06:00
PMCR- 2016/08/29
CRDT- 2016/08/30 06:00
PHST- 2016/06/08 00:00 [received]
PHST- 2016/08/16 00:00 [accepted]
PHST- 2016/08/30 06:00 [entrez]
PHST- 2016/08/30 06:00 [pubmed]
PHST- 2017/08/19 06:00 [medline]
PHST- 2016/08/29 00:00 [pmc-release]
AID - PONE-D-16-19805 [pii]
AID - 10.1371/journal.pone.0162023 [doi]
PST - epublish
SO  - PLoS One. 2016 Aug 29;11(8):e0162023. doi: 10.1371/journal.pone.0162023. 
      eCollection 2016.