IL-18 is an important pro-inflammatory cytokine that binds to its receptor complex (IL-18Rα encoded by IL18R1 and IL-18Rβ encoded by IL18RAP), activating downstream MyD88/NF-κB and MAPK signaling pathways and playing key regulatory roles in innate and adaptive immunity ^[1]. Abnormal activation of the human IL-18/IL-18R signaling pathway is closely associated with various inflammatory diseases, including inflammatory bowel disease (IBD), rheumatoid arthritis (RA), psoriasis, metabolic inflammation, and regulation of the tumor immune microenvironment ^[2]. The huIL18R1/huIL18RAP humanized mouse model was generated using gene editing technology, in which the mouse Il18r1 gene region from exon 1 to the downstream region of exon 13 of Il18rap was replaced with the human IL18R1 gene region from exon 1 to the downstream region of exon 10 of IL18RAP. This model can be used to research the functional roles of human IL-18/IL-18R signaling in inflammatory responses. Its applications mainly include mechanistic studies of inflammatory bowel disease (IBD), rheumatoid arthritis (RA), psoriasis and skin inflammation, as well as metabolic disease-associated inflammation. In addition, this model can be used for exploring cancer immunotherapy strategies and evaluating the potential effects of various therapeutic approaches targeting the IL-18/IL-18R pathway in regulating intestinal inflammation, joint inflammation, skin inflammation, metabolic inflammation, and the tumor microenvironment.

Prr11 is located on chromosome 11 of mice. Nuclease Technology was used to design sgRNA; Prr11 knockout mice were obtained by applying high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.

Or5m11 is located on chromosome 2 of mice. SgRNA and ssDNA will be designed using Nuclease Technology; Or5m11 conditional knockout mice will be obtained by high-throughput electroporation of fertilized eggs. After sexual maturity, sperm will be collected for cryopreservation.