• Interleukin-20 receptor subunit beta (IL20RB) is a single-pass type I membrane protein of the type II cytokine receptor family. The interleukin-20-receptor I complex (IL-20-RI) is composed of two chains, IL20RA and IL20RB. IL-20-RI is a receptor for IL-19, IL-20 and IL-24. IL20RB can also form a heterodimer with IL22RA1. The IL22RA1/IL20RB dimer is a receptor for IL20 and IL24.
• Tumor cells induce osteoclasts to secrete IL-19, the ligand of IL-20RB, and IL-19 stimulates IL-20RB-expressing tumor cells to activate downstream JAK1/STAT3 signaling, thereby enhancing tumor cell proliferation in bone. Importantly, blocking IL-20RB with the neutralizing antibody LTMA1G11 significantly suppresses lung cancer bone metastasis and inhibits tumor growth.
• The exons 2–6 of the mouse Il20ra gene, which encode the extracellular domain and part of the transmembrane domain, were replaced by their human counterparts in B-hIL20RB mice. The genomic region of mouse Il20ra gene that encodes cytoplasmic portion was retained. The promoter, 5’UTR and 3’UTR region of the mouse gene were also retained. The chimeric IL20RB expression was driven by endogenous mouse Il20ra promoter, while mouse IL20RB gene transcription and translation will be disrupted.
• IL20RB were detectable in stomach, lung, liver and testis in wild-type mice and homozygous B-hIL20RB mice. The antibody was cross-reactive between human and mouse.
• Mouse Il20rb mRNA was detectable only in wild-type mice. Human IL20RB mRNA was detectable only homozygous B-hIL20RB mice but not in wild-type mice.
• Tumor cell lines inoculated in B-hIL20RB mice can be used to study the in vivo efficacy and safety evaluation of antibody drugs.

Gene targeting strategy for B-hIL20RB mice. The exons 2–6 of the mouse Il20ra gene, which encode the extracellular domain and part of the transmembrane domain, were replaced by their human counterparts in B-hIL20RB mice. The genomic region of mouse Il20ra gene that encodes cytoplasmic portion was retained. The promoter, 5’UTR and 3’UTR region of the mouse gene were also retained. The chimeric IL20RB expression was driven by endogenous mouse Il20ra promoter, while mouse IL20RB gene transcription and translation will be disrupted.

Strain specific analysis of IL20RB mRNA expression in wild-type C57BL/6JNifdc mice and B-hIL20RB mice by RT-PCR. Stomach RNA were isolated from wildtype C57BL/6 mice (+/+) and homozygous B-hL20RB mice (H/H), then cDNA libraries were synthesized by reverse transcription, followed by PCR with mouse or human IL20RB primers. Mouse Il20rb mRNA was detectable only in wild-type mice. Human IL20RB mRNA was detectable only homozygous B-hIL20RB mice but not in wild-type mice.

Western blot analysis of IL20RB protein expression in homozygous B-hIL20RB mice. Various tissue lysates were collected from wild-type C57BL/6JNifdc (+/+) mice and homozygous B-hIL20RB mice (H/H), and then analyzed by western blot with anti-IL20RB antibody (Proteintech, 20521-1-AP ). 40 μg total proteins were loaded for western blotting analysis. IL20RB were detectable in stomach, lung, liver and testis in wild-type mice and homozygous B-hIL20RB mice. The antibody was cross-reactive between human and mouse.