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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
Author(s) -
Kim Mi-Young,
Ahn Kyu Youn,
Lee Seon Min,
Koh Jeong Tae,
Chun Byeong Jo,
Bae Choon Sang,
Lee Kee Sook,
Kim Kyung Keun
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.03.106
Subject(s) - transgene , biology , enhancer , genetically modified mouse , promoter , microbiology and biotechnology , transcription factor , gene expression , gene , hippocampus , genetics , neuroscience
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.