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The promoter of brain-specific angiogenesis inhibitor 1-associated protein 4 drives developmentally targeted transgene expression mainly in adult cerebral cortex and hippocampus

Authors
 Mi-Young Kim  ;  Kyu Youn Ahn  ;  Kyung Keun Kim  ;  Kee Sook Lee  ;  Choon Sang Bae  ;  Byeong Jo Chun  ;  Jeong Tae Koh  ;  Seon Min Lee 
Citation
 FEBS LETTERS, Vol.566(1-3) : 87-94, 2004 
Journal Title
 FEBS LETTERS 
ISSN
 0014-5793 
Issue Date
2004
MeSH
Animals ; Animals, Newborn ; Base Sequence ; Binding Sites ; Cell Adhesion Molecules, Neuronal/genetics* ; Cerebral Cortex/cytology ; Cerebral Cortex/metabolism ; Cerebral Cortex/physiology* ; Gene Expression Regulation, Developmental ; Hippocampus/cytology ; Hippocampus/metabolism ; Hippocampus/physiology* ; Humans ; Lac Operon/genetics ; Mice ; Mice, Transgenic ; Neurons/metabolism ; Promoter Regions, Genetic/genetics ; Tissue Distribution ; Transcription Initiation Site ; Transcription, Genetic/genetics* ; Transgenes ; beta-Galactosidase/metabolism
Keywords
BAI1-AP4 ; brain-specific angiogenesis inhibitor 1-associated protein 4 ; HSV-TK ; herpes simplex virus-thymidine kinase ; NSE ; neuron-specific enolase ; TG ; transgenic ; BAI1-AP4 promoter ; Neuron-specific expression ; Transgene ; Developmental expression
Abstract
Restricting transgene expression to specific cell types and maintaining long-term expression are major goals for gene therapy. Previously, we cloned brain-specific angiogenesis inhibitor 1-associated protein 4 (BAI1-AP4), a novel brain-specific protein that interacts with BAI1, and found that it was developmentally upregulated in the adult brain. In this report, we isolated 5 kb of the 5′ upstream sequence of the mouse BAI1-AP4 gene and analyzed its promoter activity. Functional analyses demonstrated that an Sp1 site was the enhancer, and the region containing the transcription initiation site and an AP2-binding site was the basal promoter. We examined the ability of the BAI1-AP4 promoter to drive adult brain-specific expression by using it to drive lacZ expression in transgenic (TG) mice. Northern blot analyses showed a unique pattern of β-galactosidase expression in TG brain, peaking at 1 month after birth, like endogenous BAI1-AP4. Histological analyses demonstrated the same localization and developmental expression of β-galactosidase and BAI1-AP4 in most neurons of the cerebral cortex and hippocampus. Our data indicate that TG mice carrying the BAI1-AP4 promoter could be a valuable model system for region-specific brain diseases.
Files in This Item:
T200404827.pdf Download
DOI
10.1016/j.febslet.2004.03.106
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Mi Young(김미영)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/113005
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