Interleukin-18 (IL18) is a pro-inflammatory cytokine primarily secreted by macrophages, dendritic cells, and keratinocytes. It is a member of the IL-1 superfamily and plays an important regulatory role in both innate and adaptive immune responses ^[1]. IL18 binds to the IL18 receptor (IL18R) and, in synergy with IL12, induces Th1 cells to produce interferon-γ (IFN-γ), promoting the activation and proliferation of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, while also participating in the regulation of inflammasome-mediated inflammatory responses ^[2-3]. The IL18 gene is located on human chromosome 11 and is closely associated with the development of various autoimmune diseases, infectious diseases, and cancers. It has emerged as an important target for tumor immunotherapy, infectious vaccine development, and drug research for autoimmune diseases ^[4-5]. The huIL18 mouse is a humanized model constructed by gene-editing technology, in which the sequence from the start codon to the stop codon of the mouse endogenous Il18 gene is replaced with the corresponding sequence of the human IL18 gene. This model is suitable for evaluating the efficacy and safety of IL18-targeted antibodies and CAR-cell therapies, as well as for preclinical studies in tumor immunity, infectious disease vaccines, autoimmune disorders, and metabolic and cardiovascular diseases.

Padi3 is located on chromosome 4 of mice. Nuclease Technology will be used to design sgRNA; Padi3 knockout mice will be obtained by applying high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.

Vmn1r82 is located on chromosome 7 of mice. SgRNA and ssDNA will be designed using Nuclease Technology; Vmn1r82 conditional knockout mice will be obtained by high-throughput electroporation of fertilized eggs. After sexual maturity, sperm will be collected for cryopreservation.