The promoter of brain-specific angiogenesis inhibitor 1-associated protein 4 drives developmentally targeted transgene expression mainly in adult cerebral cortex and hippocampus.
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.
Kim
Mi-Young
MY
Medical Research Center for Gene Regulation, Chonnam National University Medical School, Hak-Dong 5, Dong-Ku, Kwangju 501-190, South Korea.
Ahn
Kyu Youn
KY
Lee
Seon Min
SM
Koh
Jeong Tae
JT
Chun
Byeong Jo
BJ
Bae
Choon Sang
CS
Lee
Kee Sook
KS
Kim
Kyung Keun
KK
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
D015816:Cell Adhesion Molecules, Neuronal; D001616:beta-Galactosidase