The IL18BP (Interleukin 18 Binding Protein) gene encodes a secreted, high-affinity, naturally occurring antagonist of the proinflammatory cytokine Interleukin-18 (IL-18), functioning by binding IL-18 to prevent it from interacting with its receptor, thereby inhibiting IL-18-induced immune responses, such as interferon-gamma (IFN-γ) production ^[1]. The gene's protein, IL-18BP, is constitutively expressed and secreted primarily by mononuclear cells (such as monocytes/macrophages and T-cells) and is widely expressed at the RNA level in numerous tissues, including the spleen, lung, placenta, and small intestine ^[2]. Its expression can be enhanced by IFN-γ in a negative feedback loop to regulate inflammation ^[3]. Dysregulation or an imbalance in the ratio of IL-18 to IL-18BP is associated with a range of inflammatory and autoimmune conditions, including Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus (SLE), systemic juvenile idiopathic arthritis (SJIA), fulminant viral hepatitis, and adult-onset Still's disease. The B6-huIL18BP mouse is a humanized model constructed through gene-editing technology, in which the sequences from the ATG start codon to the TAA stop codon of the endogenous mouse Il18bp gene are replaced with the sequences from the ATG start codon to the TAA stop codon of the human IL18BP gene. This model can be used for research on tumor mechanisms and tumor immunotherapy, inflammatory and autoimmune conditions, as well as for the development of IL18BP-targeted drugs.

Tcfl5 is located on chromosome 2 of mice. SgRNA and ssDNA were designed using Nuclease Technology; Tcfl5 conditional knockout mice were obtained by high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.