Transgenic mouse for conditional, tissue-specific Cox-2 overexpression.
We constructed a cyclooxygenase-2 (Cox-2) conditional overexpression transgenic mouse (Cox-2 COE). The transgene contains a CAG promoter driving the Cox-2 and humanized Renilla luciferase (hRL) coding regions, linked by an internal ribosomal entry site. The promoter is followed by a loxP-flanked sequence containing enhanced green fluorescent protein (EGFP), a neomycin selection cassette, and a transcriptional/translational STOP sequence. In the presence of Cre recombinase the loxP-flanked sequence is excised. Cox-2/hRL expression can be monitored repeatedly and noninvasively in vivo by imaging hRL activity. To demonstrate conditional Cox-2 and hRL expression, a nonreplicating adenovirus carrying Cre recombinase (Ad.CMV.Cre) was injected intravenously; hepatic Cox-2 expression and hRL signal were elevated. Cox-2 COE embryonic fibroblasts express both Cox-2 and hRL following Ad.CMV.Cre infection. PGE(2) production is also increased following Ad.CMV.Cre infection of Cox-2 COE embryo fibroblasts. Cox-2 COE mice should be valuable for the study of Cox-2 overexpression in cardiovascular disease, acute and chronic inflammatory responses, neurodegenerative diseases, and cancer.
Kamei
Ken-ichiro
K
Department of Molecular and Medical Pharmacology, Molecular Biology Institute, Crump Institute for Molecular Imaging, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
Ishikawa
Tomo-o
TO
Herschman
Harvey R
HR
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D051546:Cyclooxygenase 2 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism; D017353:Gene Deletion; D005786:Gene Expression Regulation; D005821:Genetic Techniques; D005822:Genetic Vectors / Q000008:administration & dosage; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007275:Injections, Intravenous; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D049410:Luciferases, Renilla / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008957:Models, Genetic; D011401:Promoter Regions, Genetic; D019076:Transgenes; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
D014764:Viral Proteins; D049452:Green Fluorescent Proteins; D049410:Luciferases, Renilla; D051546:Cyclooxygenase 2; C045073:Cre recombinase; D019426:Integrases