The interleukin-1 receptor accessory protein, encoded by IL1RAP, serves as a critical co-receptor for multiple cytokine systems, notably the interleukin-1 (IL-1) family. This broadly expressed protein is essential for the formation of functional receptor complexes for IL-1, IL-33, and IL-36, thereby mediating downstream signaling pathways that drive innate immunity and inflammatory responses ^[1-5]. Acting as a co-receptor, IL1RAP interacts with ligand-binding receptors such as IL1R1, IL33R (IL1RL1/ST2), and IL36R, initiating MyD88-dependent signal transduction that culminates in the expression of pro-inflammatory genes and cytokines ^[1-5]. IL1RAP expression is observed across a range of cell types, including immune, endothelial, epithelial, and neuronal cells, as well as various tumor lineages. Perturbations in IL1RAP expression or genetic variants have been implicated in a spectrum of pathologies, encompassing inflammatory diseases such as asthma, autoimmune disorders, neurodegenerative conditions such as Alzheimer's disease, and malignancies including acute myeloid leukemia, Ewing sarcoma, pancreatic cancer, and gastric adenocarcinoma ^[2-4]. Consequently, IL1RAP represents a target of intense investigation for therapeutic interventions in cancer and inflammatory diseases ^[4-5]. hIL1RAP mice are humanized models generated using gene editing technology. They are constructed by integrating the protein-coding sequence (CDS) encoding the extracellular domain of human IL1RAP protein and the intracellular domain of mouse IL1RAP protein, along with the 3'UTR of the mouse Il1rap gene, into a specific site within the mouse Il1rap gene. This process retains the endogenous gene sequence encoding the mouse signal peptide. Homozygous hIL1RAP mice are viable and fertile. This model can be used for studying the pathological mechanisms and therapeutic approaches of cancer and inflammatory diseases, and for the development of IL1RAP-targeted drugs.

Reg3b is located on chromosome 6 of mice. Nuclease Technology was used to design sgRNA; Reg3b knockout mice were obtained by applying high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.

Marcks is located on chromosome 10 of mice. SgRNA and ssDNA will be designed using Nuclease Technology; Marcks conditional knockout mice will be obtained by high-throughput electroporation of fertilized eggs. After sexual maturity, sperm will be collected for cryopreservation.