Isolation of a regulatory region of activin receptor-like kinase 1 gene sufficient for arterial endothelium-specific expression.
Activin receptor-like kinase 1 (Acvrl1; Alk1) is a type I receptor for transforming growth factor-beta (TGF-beta). ALK1 plays a pivotal role in vascular development and is involved in the development of hereditary hemorrhagic telangiectasia 2 (HHT2), a dominantly inherited vascular disorder, and pulmonary hypertension. We have previously shown that Alk1 is expressed predominantly in arterial endothelial cells (ECs). Despite recent discoveries of a number of artery-specific genes, the regulatory elements of these genes have not been characterized. To investigate the cis-acting elements essential for the artery-specific Alk1 expression, we have generated a series of transgenic constructs with various lengths and regions of Alk1 genomic fragments connected to a LacZ reporter gene, and analyzed the reporter gene expression in transgenic mice. We found that a 9.2-kb genomic fragment, which includes 2.7-kb promoter region and the entire intron 2, is sufficient to drive arterial endothelium-specific expression. The defined regulatory region, as well as the transgenic mouse lines, would be invaluable resources in studying the mechanisms underlying angiogenesis, arteriogenesis, and vascular disorders, such as HHT and pulmonary hypertension. The full text of this article is available online at http://circres.ahajournals.org.
Seki
Tsugio
T
Department of Physiology and Functional Genomics, University of Florida,Gainesville, Fla 32610, USA.
Hong
Kwon-Ho
KH
Yun
Jihye
J
Kim
Seong-Jin
SJ
Oh
S Paul
SP
D030201:Activin Receptors, Type I / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D030301:Activin Receptors, Type II; D000818:Animals; D001158:Arteries / Q000166:cytology / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D001665:Binding Sites; D016384:Consensus Sequence; D004730:Endothelium, Vascular / Q000378:metabolism*; D005091:Exons / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D006801:Humans; D007438:Introns / Q000235:genetics; D007763:Lac Operon; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000235:genetics; D009928:Organ Specificity; D011401:Promoter Regions, Genetic / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D016415:Sequence Alignment; D017385:Sequence Homology; D012867:Skin / Q000293:injuries; D013045:Species Specificity; D014157:Transcription Factors / Q000378:metabolism; D014945:Wound Healing / Q000235:genetics
D014157:Transcription Factors; C425364:ACVRL1 protein, human; D030201:Activin Receptors, Type I; D030301:Activin Receptors, Type II; C498931:Acvrl1 protein, mouse