CDH17 (Cadherin 17), a member of the cadherin superfamily encoded by the CDH17 gene, is also known as liver-intestine cadherin (LI-cadherin). It is primarily expressed in the epithelial cells of the digestive tract, such as the small intestine and colon, and plays a crucial role in cell adhesion, maintenance of the epithelial barrier, and intestinal tissue homeostasis ^[1-2]. Studies have shown that CDH17 is abnormally overexpressed in various gastrointestinal tumors, including gastric, colorectal, pancreatic, and hepatocellular carcinomas. Its expression is closely associated with tumor proliferation, invasion, metastasis, and poor prognosis, making it a promising potential therapeutic target ^[2-4]. Currently, research involving CDH17-targeting monoclonal antibodies, antibody-drug conjugates (ADCs), and CAR-T/CAR-NK cell therapies is underway to explore their potential in the targeted treatment of gastrointestinal cancers ^[3-5]. The hCDH17 mouse is a humanized model generated via gene editing. In this model, the region from aa.28 in exon 3 to partial intron 3 of the mouse Cdh17 was replaced with Mature Chimeric CDH17 CDS-3’UTR of the mouse Cdh17-WPRE-BGH pA cassette. The murine signal peptide was preserved. This model is suitable for evaluating the in vivo efficacy and safety of CDH17-targeting monoclonal antibodies, ADCs, and CAR-T/CAR-NK cell therapies. It is also applicable for research into the mechanisms of gastrointestinal tumor development, the tumor immune microenvironment, and combination therapeutic strategies.

Rad51c is located on chromosome 11 of mice. SgRNA and ssDNA will be designed using Nuclease Technology; Rad51c conditional knockout mice will be obtained by high-throughput electroporation of fertilized eggs. After sexual maturity, sperm will be collected for cryopreservation.