德晋贵宾厅

• IL-23 is a heterodimeric cytokine composed of p40 and p19 subunits, primarily produced by macrophages and dendritic cells. IL-23 binds to its receptor IL-23R, which regulates the release of downstream pro-inflammatory cytokines.
• The genome of the mouse Il23a gene encoding the full-length protein was replaced with human IL23A counterpart in B-hIL23A/hIL12B, Rag2 KO mice. The genome of the mouse Il12b gene encoding the full-length protein was replaced with human IL12B counterpart in B-hIL23A/hIL12B, Rag2 KO mice. The exon 3 and 3’UTR region of mouse Rag2 were knocked out in B-hIL23A/hIL12B, Rag2 KO mice, resulting in a disruption of the Rag2 gene.
• In T cells transfer induced colitis in B-hIL23A/hIL12B, Rag2 KO mice (Donor: B-hIL23R/hIL12RB1 plus mice), treatment with of anti-human IL12/IL23p40 antibody Ustekinumab, anti-human IL23p19 antibody Guselkumab and anti-human IL23R oral peptide Icotrokinra improved the disease characteristics of colitis.
• This product is used for the evaluation of the pharmacodynamics of anti- anti-human IL12/IL23p40 antibody, anti-human IL23p19 antibody and anti-human IL23R test article in autoimmune diseases such as inflammatory bowel disease.

Gene targeting strategy for B-hIL23A/hIL12B, Rag2 KO mice.

The exons 1-4 of mouse Il23a gene that encode the whole molecule (ATG to STOP codon) were replaced by human counterparts in B-hIL23A/hIL12B, Rag2 KO mice. The promoter, 5’UTR and 3’UTR region of the mouse gene were retained. The human IL23A expression was driven by endogenous mouse Il23a promoter, while mouse Il23a gene transcription and translation will be disrupted.

The exons 2-8 of mouse Il12b gene that encode the whole molecule (ATG to STOP codon), including 3’UTR were replaced by human counterparts in B-hIL23A/hIL12B, Rag2 KO mice. The promoter and 5’UTR region of the mouse gene were retained. The human IL12B expression was driven by endogenous mouse Il12b promoter, while mouse Il12b gene transcription and translation will be disrupted.

The exon 3 and 3’UTR region of mouse Rag2 were knocked out in B-hIL23A/hIL12B, Rag2 KO mice, resulting in a disruption of the Rag2 gene.

CD4+CD45RB^low T and CD4+CD45RB^high T cells were isolated from the spleens of B-hIL23R/hIL12RB1 plus mice. B-hIL23A/hIL12B, Rag2 KO mice in group G1 were injected with CD4+CD45RB^low T cells, while B-hIL23A/hIL12B, Rag2 KO mice in groups G2-G5 were injected with CD4+CD45RB^high T cells. The treatment groups received anti-human IL12/IL23p40 antibody Ustekinumab (10 mpk, provided by WuXi AppTec), anti-human IL23p19 antibody Guselkumab (10 mpk, provided by WuXi AppTec) and anti-human IL23R oral peptide Icotrokinra (10 mpk, provided by WuXi AppTec). (A) Body weight change. (B) DAI score. (C) Colon index. (D) Colon photo. Administration of anti-human IL12/IL23p40 antibody Ustekinumab, anti-human IL23p19 antibody Guselkumab and anti-human IL23R oral peptide Icotrokinra effectively improved T cells transfer induced colitis. Two-way ANOVA or one-way ANOVA was used for multiple comparisons, with each group compared to Vehicle. Values are expressed as mean ± SEM. *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001.

Note: This experiment was conducted by WuXi AppTec, T cell transfer induced chronic colitis in B-hIL23A/hIL12B, Rag2 KO mice (Donor: B-hIL23R/hIL12RB1 plus mice).

CD4+CD45RB^low T and CD4+CD45RB^high T cells were isolated from the spleens of B-hIL23R/hIL12RB1 plus mice. B-hIL23A/hIL12B, Rag2 KO mice in group G1 were injected with CD4+CD45RB^low T cells, while B-hIL23A/hIL12B, Rag2 KO mice in groups G2-G5 were injected with CD4+CD45RB^high T cells. The treatment groups received anti-human IL12/IL23p40 antibody Ustekinumab (10 mpk, provided by WuXi AppTec), anti-human IL23p19 antibody Guselkumab (10 mpk, provided by WuXi AppTec) and anti-human IL23R oral peptide Icotrokinra (10 mpk, provided by WuXi AppTec). (A) H&E staining of colon tissue. (B) Pathological score. Administration of anti-human IL12/IL23p40 antibody Ustekinumab, anti-human IL23p19 antibody Guselkumab and anti-human IL23R oral peptide Icotrokinra effectively improved T cells transfer induced colitis. Two-way ANOVA or one-way ANOVA was used for multiple comparisons, with each group compared to Vehicle. Values are expressed as mean ± SEM. *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001.

Note: This experiment was conducted by WuXi AppTec, T cell transfer induced chronic colitis in B-hIL23A/hIL12B, Rag2 KO mice (Donor: B-hIL23R/hIL12RB1 plus mice).