title: The promoter of brain-specific angiogenesis inhibitor 1-associated protein 4 drives developmentally targeted transgene expression mainly in adult cerebral cortex and hippocampus.
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 beta-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 beta-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.
authors.affiliation: Medical Research Center for Gene Regulation, Chonnam National University Medical School, Hak-Dong 5, Dong-Ku, Kwangju 501-190, South Korea.
authors.forename: Mi-Young
authors.initials: MY
authors.lastname: Kim
authors.forename: Kyu Youn
authors.initials: KY
authors.lastname: Ahn
authors.forename: Seon Min
authors.initials: SM
authors.lastname: Lee
authors.forename: Jeong Tae
authors.initials: JT
authors.lastname: Koh
authors.forename: Byeong Jo
authors.initials: BJ
authors.lastname: Chun
authors.forename: Choon Sang
authors.initials: CS
authors.lastname: Bae
authors.forename: Kee Sook
authors.initials: KS
authors.lastname: Lee
authors.forename: Kyung Keun
authors.initials: KK
authors.lastname: Kim
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D001665:Binding Sites; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007763:Lac Operon / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D014018:Tissue Distribution; D024363:Transcription Initiation Site; D014158:Transcription, Genetic / Q000235:genetics*; D019076:Transgenes; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D001616:beta-Galactosidase