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Noninvasive imaging of hemorrhage‐induced global ischemia with a transgenic mouse expressing luciferase coupled to hypoxia‐inducible factor (HIF1α)
Author(s) -
Bowman Phillip,
Bynum James,
Kiang Juliann G.,
Baer David,
Johnson Joanna,
Dubick Michael
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.1038.3
Subject(s) - luciferase , ischemia , hypoxia inducible factors , shock (circulatory) , transgene , hemorrhagic shock , genetically modified mouse , hypoxia (environmental) , pathology , reporter gene , chemistry , medicine , microbiology and biotechnology , biology , gene , oxygen , gene expression , biochemistry , transfection , organic chemistry
Hemorrhagic shock leads to global ischemia, but available blood is distributed unevenly to the body's organs and it is generally accepted that blood is shunted to those organs that maintain critical functions. The organs that become most ischemic and their role in hemorrhagic shock, however, have not been determined. We used the recently described, genetically engineered mouse FVB.129S6‐Gt(ROSA)26Sortm1(HIF1α/luc) Kael/J* (Jackson Laboratories) which has a luciferase gene fused to the region of HIF1α that binds to von Hippel‐Lindau protein in an oxygen‐dependent manner generating a reporter that can be used to monitor oxygen availability in intact tissues. Thus more light would be emitted from ischemic tissue. To determine if this mouse could be used to identify organs affected by hemorrhagic shock, 40 per cent of the calculated blood volume was removed via the submaxillary vein, and the mice were injected with luciferin, anesthetized with isoflurane, and imaged in the Xenogen IVIS 100 Imaging system as a function of time after hemorrhage. The ventral surface of these mice exhibited increased light emitted from the region of the intestine that was most prominent at 3‐6 h after hemorrhage but still evident at 72 h. This technique should allow more detailed studies of those tissues most affected by hemorrhagic shock. *Safran, M.,et. al., Proc Natl Acad Sci U S A 2006;103:105‐110.