• 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 sTL1A/DR3. In addition, DcR3 can inhibit apoptosis, reduce inflammation, and prevent tissue damage by neutralizing LIGHT and FasL.
• 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-hTL1A plus/hIL23A/hIL12B mice. The genome of the mouse Il12b gene encoding the full-length protein was replaced with human IL12B counterpart in B-hTL1A plus/hIL23A/hIL12B mice.
• Soluble human TL1A and human IL23 were exclusively detectable in homozygous B-hTL1A plus/hIL23A/hIL12B mice, but not in wild-type C57BL/6JNifdc mice.
• This product is used for pharmacological and safety evaluation of autoimmune diseases such as Inflammatory bowel disease, psoriasis and arthritis.

Gene targeting strategy for B-hTL1A plus/hIL23A/hIL12B mice.

The targeting strategy for humanized TL1A in B-hTL1A plus/hIL23A/hIL12B mice is currently kept confidential.

The exons 1-4 of mouse Il23a gene that encode the whole molecule (ATG to STOP codon) were replaced by human counterparts in B-hTL1A plus/hIL23A/hIL12B 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-hTL1A plus/hIL23A/hIL12B 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.

B-hTL1A plus/hIL23A/hIL12B mice were derived from mating B-hTL1A mice plus (112949) and B-hIL23A/hIL12B mice (120553).

Soluble TL1A expression analysis in B-hTL1A plus/hIL23A/hIL12B mice by ELISA. Bone marrow-derived dendritic cells were isolated from wild-type C57BL/6JNifdc mice (+/+), homozygous B-hTL1A plus/hIL23A/hIL12B mice (H/H;H/H;H/H) and homozygous B-hTL1A/hIL23A/hIL12B mice (H/H;H/H;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 C57BL/6JNifdc mice. Soluble human TL1A was exclusively detectable in homozygous B-hTL1A plus/hIL23A/hIL12B mice and homozygous B-hTL1A/hIL23A/hIL12B mice. ND: not detectable.

Mouse IL-23 and human IL-23 expression analysis in B-hTL1A plus/hIL23A/hIL12B mice by ELISA. Bone marrow derived dendritic cells were produced by culturing the bone marrow from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hTL1A plus/hIL23A/hIL12B mice (H/H;H/H;H/H), which were stimulated with 1 μg/mL LPS in vitro. After stimulation, the supernatants were collected and the levels of mouse and human IL23 were analyzed by ELISA. Mouse IL23 was only detectable in wild-type C57BL/6JNifdc mice. Human IL23 was exclusively detectable in homozygous B-hTL1A plus/hIL23A/hIL12B mice. Values are expressed as mean ± SEM. ND: not detectable.