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.