• TL1A binds to death receptor 3 (DR3) to provide stimulatory signals for downstream signaling pathways, thereby regulating the proliferation, activation, apoptosis of effector cells, and the production of cytokines and chemokines. Soluble decoy receptor 3 (DcR3) may neutralize the effects of soluble TL1A (sTL1A)/DR3. In addition, DcR3 can inhibit apoptosis, reduce inflammation, and prevent tissue damage by neutralizing LIGHT and FasL.
• The exons 1-4 of mouse Tl1a gene that encode extracellular domain were replaced by human counterparts in B-hTL1A mice(CB-17 SCID).
• Human TL1A was only detectable in homozygous B-hTL1A mice(CB-17 SCID).
• Humanization of TL1A does not change the overall frequency or distribution of immune cell types in spleen and blood.
• This product is used for pharmacodynamics and safety evaluation of  drugs.

Gene targeting strategy for B-hTL1A mice(CB-17 SCID). The exons 1-4 of mouse Tl1a gene that encode extracellular domain were replaced by human counterparts in B-hTL1A mice(CB-17 SCID). The genomic region of mouse Tl1a gene that encodes transmembrane domain and cytoplasmic portion was retained. The promoter, 5’UTR and 3’UTR region of the mouse gene were also retained. The chimeric TL1A expression was driven by endogenous mouse Tl1a promoter, while mouse Tl1a gene transcription and translation would be disrupted.

Soluble TL1A expression analysis in B-hTL1A mice(CB-17 SCID) by ELISA. Bone marrow-derived dendritic cells were isolated from wild-type CB-17 SCID mice (+/+) and homozygous B-hTL1A mice(CB-17 SCID) (H/H), and stimulated with 1 μg/mL LPS  in vitro for 24 h, then the supernatants were collected and the levels of soluble TL1A were measured using a species-specific mouse and human TL1A ELISA kit. Soluble mouse TL1A was detectable in wild-type CB-17 SCID mice. Soluble human TL1A was exclusively detectable in homozygous B-hTL1A mice(CB-17 SCID). Values are expressed as mean ± SEM. ND: not detectable.

Frequency of leukocyte subpopulations in spleen by flow cytometry. Splenocytes were isolated from wild-type CB-17 SCID mice(female, n=3, 8-week-old) and homozygous B-hTL1A mice(CB-17 SCID) (female, n=3, 8-week-old). A. Flow cytometry analysis of the splenocytes was performed to assess the frequency of leukocyte subpopulations. B. Frequency of T cell subpopulations. Frequencies of T cells, B cells, NK cells, DCs, neutrophils, monocytes, macrophages, CD4+ T cells, CD8+ T cells and Tregs in B-hTL1A mice(CB-17 SCID) were similar to those in CB-17 SCID mice, demonstrating that humanization of TL1A does not change the frequency or distribution of these cell types in spleen. Values are expressed as mean ± SEM.

Frequency of leukocyte subpopulations in blood by flow cytometry. Blood cells were isolated from wild-type CB-17 SCID mice (female, n=3, 8-week-old) and homozygous B-hTL1A mice(CB-17 SCID) (female, n=3, 8-week-old). A. Flow cytometry analysis of the blood cells was performed to assess the frequency of leukocyte subpopulations. B. Frequency of T cell subpopulations. Percentages of T cells, B cells, NK cells, dendritic cells, neutrophils, monocytes, macrophages, CD4+ T cells, CD8+ T cells and Tregs in B-hTL1A mice(CB-17 SCID) were similar to those in CB-17 SCID mice, demonstrating that humanization of TL1A does not change the frequency or distribution of these cell types in blood. Values are expressed as mean ± SEM.