Description

• 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.
• The genome of mouse Tl1a encoding the extracellular domain was replaced by human counterparts in B-hTL1A mice(C).
• Human TL1A protein and RNA were detectable in homozygous B-hTL1A mice(C).
• This product is used for the evaluation of the pharmacodynamics and safety of anti-human TL1A antibodies in autoimmune diseases such as inflammatory bowel disease.

Targeting strategy

Gene targeting strategy for B-hTL1A mice(C).The exons 1-4 of mouse Tl1a gene that encode extracellular domain were replaced by human counterparts in B-hTL1A mice(C). 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 will be disrupted.

mRNA expression analysis

Strain specific analysis of TL1A gene expression in wild-type (WT) mice and B-hTL1A mice(C) by RT-PCR. Mouse Tl1a mRNA was detectable only in lung and colon of wild-type BALB/c mice (+/+). Human TL1A mRNA was detectable only in homozygous B-hTL1A mice(C) (H/H) but not in wild-type BALB/c mice (+/+) .

Protein expression analysis

Soluble TL1A expression analysis in B-hTL1A mice(C) by ELISA. Bone marrow derived dendritic cells (BMDCs) were produced by culturing the bone marrow from wild-type BALB/c mice (+/+) and homozygous B-hTL1A mice(C) (H/H), which were stimulated with LPS in vitro. After stimulation, the supernatants were collected and the levels of soluble TL1A were measured using a species-specific human TL1A ELISA kit (R&D, DY1319-05). Soluble human TL1A was exclusively detectable in homozygous B-hTL1A mice(C) but not wild-type BALB/c mice. Values are expressed as mean ± SEM. ND: not detectable.