B6-hROR1 Mouse

The receptor tyrosine kinase-like orphan receptor 1 (ROR1) gene encodes a transmembrane protein that is critical during embryonic development but is barely expressed in healthy adult tissues. As a carcinoembryonic antigen, the ROR1 protein functions as a receptor for the Wnt5a ligand, playing a key role in the formation of bones, lungs, and the nervous system by regulating cell migration, polarity, and proliferation. Although its expression becomes silenced after birth, ROR1 is re-expressed in various malignant tumors and conditions—including chronic lymphocytic leukemia (CLL), breast cancer, ovarian cancer, melanoma, and lung adenocarcinoma—and drives cancer progression by promoting tumor survival, metastasis, and therapeutic resistance. This tumor-specific expression profile, coupled with limited expression in normal adult tissues, reduces the risk of off-target effects, making ROR1 a desirable target in cancer drug development. Currently, multiple ROR1-targeted therapeutic strategies are in clinical trials, including monoclonal antibodies, antibody-drug conjugates (ADCs) such as zilovertamab vedotin (which precisely delivers potent toxins to ROR1-positive cancer cells), and chimeric antigen receptor (CAR) T-cell therapies that specifically recognize and eliminate ROR1-expressing tumors ^[1-2].

B6-hROR1 mouse is a humanized model constructed by replacing exon 2 and partial intron 2 of the mouse Ror1 gene with the ROR1 chimeric CDS of exons 2~9-3’UTR of mouse Ror1-WPRE-BGH pA expression cassette. The murine signal peptide of Ror1 was preserved. This model is applicable to research on tumor biology and pathological mechanisms, tumor immunotherapy studies, as well as the screening, development, and safety evaluation of ROR1-targeted drugs.