• LY6E, also known as RIGE, SCA2, RIG-E, SCA-2, TSA-1, is a surface protein belonging to the LY6/uPAR/α-neurotoxin superfamily. Structurally, it features a small extracellular domain rich in cysteine residues, lacks both transmembrane and intracellular signaling domains, and is tethered to the plasma membrane via a GPI anchor.
• Under physiological conditions, LY6E is primarily expressed in immune cells and certain epithelial tissues, where it contributes to immune homeostasis and antiviral responses, particularly through marked upregulation following interferon stimulation, modulating type I interferon signaling and viral entry processes. However, in multiple malignancies, including pancreatic cancer, non-small cell lung cancer (NSCLC), and breast cancer, LY6E exhibits aberrant overexpression that is strongly associated with enhanced tumor invasiveness, increased metastatic potential, and poor clinical prognosis. Functional studies demonstrate that LY6E promotes tumor cell proliferation and survival by regulating cell adhesion, migration, and key signal transduction pathways.
• The exons 3-4 of mouse Ly6e gene that encode the extracellular domain were replaced by human LY6E exons 3-4 in B-NDG hLY6E mice.
• Human LY6E was detectable in brain, lung, spleen, kidney and liver from homozygous B-NDG hLY6E mice.
• Application: B-NDG hLY6E mice can be used as a preclinical disease model to evaluate the in vivo efficacy and safety of drugs targeting human LY6E.

Gene targeting strategy for B-NDG hLY6E mice. The exons 3-4 of mouse Ly6e gene that encode the mature protein of LY6E were replaced by human counterparts in B-NDG hLY6E mice. The promoter, 5’UTR, signal peptide, propeptide and 3’UTR region of the mouse gene are retained. The chimeric LY6E expression is driven by endogenous mouse Ly6e promoter, while mouse Ly6e gene transcription and translation will be disrupted.

Strain specific LY6E expression analysis in homozygous B-NDG hLY6E mice by Western blot. Various tissue lysates were collected from wild-type B-NDG mice (+/+) and homozygous B-NDG hLY6E mice (H/H), analyzed by western blot with species-specific anti-human LY6E antibody (abcam, ab300399). Human LY6E was detectable in brain, lung, spleen, kidney and liver of homozygous B-NDG hLY6E mice, but not in the tissues of wild-type B-NDG mice.