title: Novel genetic approach for in vivo vascular imaging in mice.
abstract: BACKGROUND
  The formation and maintenance of a functional vasculature is essential for normal embryonic development, and genetic changes that affect the vasculature underlie pathogenesis in many human diseases. In vivo imaging in mouse models is required to understand the full complexity of mammalian vascular formation, which is a dynamic and 3-dimensional process. Optical microscopy of genetically expressed fluorescent reporter proteins offers high resolution but limited depth of penetration in vivo. Conversely, there are a plethora of molecular probes for alternative in vivo vascular imaging modalities, but few options for genetic control of contrast enhancement.
  
  
  OBJECTIVE
  To develop a reporter system for multimodal imaging of genetic processes involved in mammalian vascular biology.
  
  
  RESULTS
  To approach this problem, we developed an optimal tagging system based on Biotag-BirA technology. In the resulting Biotag reporter system, coexpression of 2 interacting proteins results in biotin labeling of cell membranes, thus enabling multimodal imaging with "avidinated" probes. To assess this approach for in vivo imaging, we generated transgenic mice that expressed the Biotag-BirA transgene from a minimal Tie2 promoter. A variety of imaging methods were used to show the utility of this approach for quantitative analysis in embryonic and adult models of vascular development, using intravascular injection of avidinated probes for near infrared, ultrasound, and magnetic resonance imaging.
  
  
  CONCLUSIONS
  The present results demonstrate the versatility of the Biotag system for studies of vascular biology in genetically engineered mice, providing a robust approach for multimodal in vivo imaging of genetic processes in the vasculature.
authors.affiliation: Kimmel Center for Biology & Medicine at the Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Ave, New York, NY 10016, USA.
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Bartelle
authors.forename: César A
authors.initials: CA
authors.lastname: Berríos-Otero
authors.forename: Joe J
authors.initials: JJ
authors.lastname: Rodriguez
authors.forename: Anne E
authors.initials: AE
authors.lastname: Friedland
authors.forename: Orlando
authors.initials: O
authors.lastname: Aristizábal
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Turnbull
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001709:Biotechnology / Q000379:methods; D001710:Biotin / Q000235:genetics / Q000378:metabolism; D001808:Blood Vessels / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism; D004622:Embryo, Mammalian / Q000098:blood supply* / Q000196:embryology* / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics*; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D042787:Receptor, TIE-2
chemical_list: D015415:Biomarkers; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D049452:Green Fluorescent Proteins; D001710:Biotin; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2; C079086:Tek protein, mouse