• IGSF8 (Immunoglobulin Superfamily Member 8) is a tetraspanin-associated protein involved in cell adhesion, immune regulation, and tumor progression. It is widely expressed across tissues and modulates cell–cell interactions through binding to tetraspanins such as CD9 and CD81. Emerging evidence suggests that IGSF8 contributes to tumor growth and immune evasion, making it a potential therapeutic target. Current strategies under exploration include monoclonal antibodies, antibody–drug conjugates, and bispecific antibodies that interfere with IGSF8-mediated signaling or promote immune clearance of tumor cells.
• The part of exon 2, exons 3-5 and part of exon 6 of mouse Igsf8 gene that encode extracellular domain were replaced by human counterparts in B-hIGSF8 mice. The genomic region of mouse Igsf8 gene that encodes signal peptide, transmembrane domain and cytoplasmic portion was retained. The promoter, 5’UTR and 3’UTR region of the mouse gene were also retained. The IGSF8 expression was driven by endogenous mouse Igsf8 promoter, while mouse Igsf8 gene transcription and translation will be disrupted.
• Human IGSF8 mRNA was exclusively detectable in homozygous B-hIGSF8 mice but not in wild-type mice.
• B-hIGSF8 mice can be used to study the in vivo efficacy and safety evaluation of drugs.

Gene targeting strategy for B-hIGSF8 mice. The part of exon 2, exons 3-5 and part of exon 6 of mouse Igsf8 gene that encode extracellular domain were replaced by human counterparts in B-hIGSF8 mice. The genomic region of mouse Igsf8 gene that encodes signal peptide, transmembrane domain and cytoplasmic portion was retained. The promoter, 5’UTR and 3’UTR region of the mouse gene were also retained. The IGSF8 expression was driven by endogenous mouse Igsf8 promoter, while mouse Igsf8 gene transcription and translation will be disrupted.

Strain specific analysis of IGSF8 mRNA expression in wild-type C57BL/6 mice and B-hIGSF8 mice by RT-PCR. Brain RNA were isolated from wild-type C57BL/6 mice (+/+) and homozygous B-hIGSF8 mice (H/H), then cDNA libraries were synthesized by reverse transcription, followed by PCR with mouse or human IGSF8 primers. Mouse Igsf8 mRNA was only detectable in wild-type mice. Human IGSF8 mRNA was exclusively detectable in homozygous B-hIGSF8 mice but not in wild-type mice.