Basic Information
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Description
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- IL21R is a type I transmembrane receptor protein that interacts with cytokine IL-21 and is mainly expressed in spleen, thymus, lymph nodes and peripheral blood lymphocytes. IL-21R knockout mice were viable and fertile, but the serum IgG1 level was decreased and IgE level was significantly upregulated in the antigenic response. Although IL-21R deficient mice did not show a deficiency of NK cells, IL-21R deficient patients showed decreased cytotoxic activity to target cells susceptible to NK cells, leading to immune deficiency disease. IL-21R has a wide range of biological functions. After binding to its ligand IL-21, it stimulates the proliferation of T cells and NK cells and regulates the survival and differentiation of B cells and dendritic cells by activating the JAKs-STATs signaling pathway, thus participating in the innate and adaptive immunity of the body. Regulating the expression level of IL-21R or blocking its signaling pathway provides a new research direction for the treatment of autoimmune diseases and tumors. BNZ-2, an antagonist targeting IL21R, is currently in the preclinical stage and is mainly used for the treatment of intestinal inflammation.
- Mouse Il21r mRNA was detectable in spleen of wild-type BALB/cCrSlcNifdc mice.
- Human IL21R mRNA was detectable in spleen of homozygous B-hIL21R mice(C).
- STAT3 phosphorylation was successfully induced with mouse IL21 or human IL21 in B cells, CD4+ T cells and CD8a+ T cells of homozygous B-hIL21R mice(C).
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Targeting strategy
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Gene targeting strategy for B-hIL21R mice(C). The exons 3~6 of mouse Il21r gene that encode extracellular domain are replaced by human counterparts in B-hIL21R mice(C). The genomic region of mouse Il21r gene that encodes signal peptide, transmembrane domain and cytoplasmic portion is retained. The promoter, 5’UTR and 3’UTR region of the mouse gene are also retained. The chimeric IL21R expression is driven by endogenous mouse Il21r promoter, while mouse Il21r gene transcription and translation will be disrupted.
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mRNA expression analysis
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Strain specific analysis of IL21R mRNA expression in wild-type BALB/cCrSlcNifdc mice and B-hIL21R mice(C) by RT-PCR. Spleen RNA were isolated from wild-type BALB/cCrSlcNifdc mice (+/+) and homozygous B-hIL21R mice(C) (H/H), then cDNA libraries were synthesized by reverse transcription, followed by PCR with mouse or human IL21R primers. Mouse Il21r mRNA was detectable in wild-type BALB/cCrSlcNifdc mice. Human IL21R mRNA was detectable only in homozygous B-hIL21R mice(C) but not in wild-type mice.
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Protein expression analysis
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Phospho Stat3 expression analysis in wild-type and homozygous mice by flow cytometry. Splenocytes from wild-type C57BL/6 and BALB/cCrSlcNifdc mice (+/+) and homozygous B-hIL21R mice and B-hIL21R mice(C) (H/H) were stimulated with mouse IL21 and human IL21 in vitro. Then the expression of p-Stat3 (BD, 557815) was analyzed by flow cytometry in B cells. Results indicated that STAT3 phosphorylation was successfully induced with mouse IL21 or human IL21 in homozygous B-hIL21R mice(C).
Phospho Stat3 expression analysis in wild-type and homozygous mice by flow cytometry. Splenocytes from wild-type C57BL/6 and BALB/cCrSlcNifdc mice (+/+) and homozygous B-hIL21R mice and B-hIL21R mice(C) (H/H) were stimulated with mouse IL21 and human IL21 in vitro. Then the expression of p-Stat3 (BD, 557815) was analyzed by flow cytometry in CD4+ T cells. Results indicated that STAT3 phosphorylation was successfully induced with mouse IL21 or human IL21 in homozygous B-hIL21R mice(C).
Phospho Stat3 expression analysis in wild-type and homozygous mice by flow cytometry. Splenocytes from wild-type C57BL/6 and BALB/cCrSlcNifdc mice (+/+) and homozygous B-hIL21R mice and B-hIL21R mice(C) (H/H) were stimulated with mouse IL21 and human IL21 in vitro. Then the expression of p-Stat3 (BD, 557815) was analyzed by flow cytometry in CD8a+ T cells. Results indicated that STAT3 phosphorylation was successfully induced with mouse IL21 or human IL21 in homozygous B-hIL21R mice(C).
