A Mouse Model of Arterial Gene Transfer Antigen-Specific Immunity Is a Minor Determinant of the Early Loss of Adenovirus-Mediated Transgene Expression

Abstract—We developed a murine model of arterial gene transfer and used it to test the role of antigen-specific immunity in the loss of adenovirus-mediated transgene expression. Adenoviral vectors encoding either β-galactosidase (β-gal) or green fluorescent protein were infused to the lumen of normal common carotids of CD-1 and C57BL/6 mice and atherosclerotic carotids of Apoe−/− mice. At 3 days after gene transfer, significant reporter gene expression was detected in all strains. Transgene expression was transient, with expression undetectable at 14 days. Next, a β-gal–expressing vector was infused into carotids of ROSA26 mice (transgenic for, and therefore tolerant of, β-gal) and RAG-2−/− mice (deficient in recombinase-activating gene [RAG]-2 and therefore lacking in antigen-specific immunity). β-Gal expression was again high at 3 days but declined substantially (>90%) by 14 days. In vivo labeling with bromodeoxyuridine revealed that carotid endothelial proliferation was increased dramatically by the ge...