Abstract
The Cre/loxP system is extensively utilized to pinpoint gene functions in specific cell types or developmental stages, typically without major disturbance to the host's genome. However, we found that the random insertion of the Mrp8-cre transgene significantly promotes the host's innate immune response. This effect is characterized by elevated susceptibility to cartilage antibody-induced arthritis, likely due to interference with genes near the insertion site. These findings underscore the potential biological disturbances caused by random transgene integration, and the necessity for stringent control strategies to avoid biased interpretations when using Cre-conditional strains.