B6-huDLL3 Mouse

The DLL3 (Delta-like canonical Notch ligand 3) gene encodes a transmembrane protein belonging to the Delta/Serrate/Lag-2 (DSL) family of ligands. Functioning within the highly conserved Notch signaling pathway, DLL3 exhibits a unique, inhibitory role, contrasting with the canonical activating function of other Notch ligands. It is believed to antagonize Notch signaling by preventing ligand-receptor interactions or by promoting receptor degradation, a mechanism critical for establishing proper cell fate decisions during development ^[1]. This is particularly evident in the formation of somites, where DLL3's function is essential for the rhythmic segmentation of the presomitic mesoderm ^[2]. While its expression is largely restricted to fetal tissues and progenitor cells in healthy adults, DLL3 is ectopically and highly expressed in a number of neuroendocrine tumors, including small cell lung cancer (SCLC), making it a promising therapeutic target. Pathogenic variants in the DLL3 gene are directly linked to Spondylocostal dysostosis type 1, a congenital disorder of vertebral segmentation ^[3].

The B6-huDLL3 mice are a humanized model constructed through gene editing technology, in which the mouse Dll3 endogenous extracellular domain is replaced with the human DLL3 extracellular domain. The murine signal peptide and transmembrane-cytoplasmic region are preserved. This model can be used for the study of the pathological mechanisms and treatment methods of DLL3-highly-expressed malignant tumors and Spondylocostal dysostosis type 1. It can also be applied to the development of DLL3-targeted drugs.