• LRIG1 is considered to be a tumor suppressor gene in humans. LRIG1 is an integral cell-surface membrane protein that is expressed by specific cells in various human tissues and that its 143-kDa form might be cleaved into 111-kDa and 32-kDa fragments. The LRIG1 protein may inhibit the growth of tumors of glial cells and the down-regulation of the LRIG1 gene may be involved in the development and progression of the tumor.
• The exons 2-15 of mouse Lrig1 gene that encode extracellular domain were replaced by human counterparts in B-hLRIG1 mice. The genomic region of mouse Lrig1 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 chimeric LRIG1 expression was driven by endogenous mouse Lrig1 promoter, while mouse Lrig1 gene transcription and translation will be disrupted.
• Mouse Lrig1 mRNA was detectable only in wild-type mice. Human LRIG1 mRNA was detectable only homozygous B-hLRIG1 mice but not in wild-type mice.
• LRIG1 was detectable in liver, brain, lung and stomach in wild-type mice and homozygous B-hLRIG1 mice. The antibody was cross-reactive between human and mouse.
• Tumor cell lines inoculated in B-hLRIG1 mice can be used to study the in vivo efficacy and safety evaluation of antibody drugs.

Gene targeting strategy for B-hLRIG1 mice. The exons 2-15 of mouse Lrig1 gene that encode extracellular domain were replaced by human counterparts in B-hLRIG1 mice. The genomic region of mouse Lrig1 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 chimeric LRIG1 expression was driven by endogenous mouse Lrig1 promoter, while mouse Lrig1 gene transcription and translation will be disrupted.

Western blot analysis of LRIG1 protein expression in homozygous B-hLRIG1 mice. Various tissue lysates were collected from wild-type C57BL/6 (+/+) mice and homozygous B-hLRIG1 mice (H/H), and then analyzed by western blot with anti-LRIG1 antibody (Proteintech, 22383-1-AP). 40 μg total proteins were loaded for western blotting analysis. LRIG1 was detectable in liver, brain, lung and stomach in wild-type mice and homozygous B-hLRIG1 mice. The antibody was cross-reactive between human and mouse.

Strain specific analysis of LRIG1 mRNA expression in wild-type C57BL/6 mice and B-hLRIG1 mice by RT-PCR. Lung RNA were isolated from wildtype C57BL/6 mice (+/+) and homozygous B-hLRIG1 mice (H/H), then cDNA libraries were synthesized by reverse transcription, followed by PCR with mouse or human LRIG1 primers. Mouse Lrig1 mRNA was detectable only in wild-type mice. Human LRIG1 mRNA was detectable only homozygous B-hLRIG1 mice but not in wild-type mice.