• CD3 consists of four protein chains (CD3E, CD3D, CD3G and CD3Z), which are important biological markers on the T cell membrane. CD3 can form a TCR/CD3 complex with the T cell receptor, participating in the regulation of T cell antigen recognition, signal transduction and T cell development.
• Cadherin 17 (CDH17) is a member of the 7D-cadherin superfamily characterized by seven cadherin repeats and a short cytoplasmic domain. It is expressed during embryogenesis in the fetal liver and gastrointestinal tract, and in adults primarily in the small intestine and colon. CDH17 plays essential roles in intercellular adhesion, tissue integrity, intestinal peptide transport, and calcium-dependent water absorption.
• Chimeric human CD3EDG were expressed, while mouse Cd3edg were knocked out in B-hCD3EDG/hCDH17 mice. The extracellular region (except signal peptide) of mouse Cdh17 was replaced by human CDH17 extracellular region sequences in B-hCD3EDG/hCDH17 mice.
• Human CD3E was exclusively detectable on T cells of  homozygous B-hCD3EDG/hCDH17 mice but not in wild-type mice.
• Human CDH17 was detected in colon and small intestine of homozygous B-hCD3EDG/hCDH17 mice.
• Application: This product is used to evaluate the pharmacodynamics and toxicity of bispecific antibody-drug conjugates (BsADCs) for treating solid tumors such as colorectal cancer, gastrointestinal cancer and others in preclinical models.

Gene targeting strategy for B-hCD3EDG/hCDH17 mice. Chimeric human CD3EDG were expressed, while mouse Cd3edg were knocked out in B-hCD3EDG/hCDH17 mice. The extracellular region (except signal peptide) of mouse Cdh17 was replaced by human CDH17 extracellular region sequences in B-hCD3EDG/hCDH17 mice.

Strain specific analysis of CD3EDG/CDH17 mRNA expression in wild-type C57BL/6JNifdc mice and B-hCDH17 mice by RT-PCR. Colon RNA were isolated from C57BL/6JNifdc mice (+/+) and homozygous B-hCD3EDG/hCDH17 mice (H/H;H/H), and then cDNA libraries were synthesized by reverse transcription, followed by PCR with mouse or human CD3E, CD3D, CD3G and CDH17 primers. Mouse Cd3e, Cd3d, Cd3g and Cdh17 mRNA was detectable only in wild-type C57BL/6JNifdc mice. Human CD3E, CD3D, CD3G and CDH17 mRNA was detectable only in homozygous B-hCD3EDG/hCDH17 mice but not in wild-type mice.

Strain specific CD3E expression analysis in homozygous B-hCD3EDG/hCDH17 mice by flow cytometry. Splenocytes(A) and blood(B) were collected from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hCD3EDG/hCDH17 mice (H/H;H/H), and analyzed by flow cytometry with species specific anti-mouse CD3E antibody (Biolegend, 100312) and anti-human CD3E antibody (BD Horizon™, 562426). Mouse CD3E was detectable in wild-type C57BL/6JNifdc mice. Human CD3E was  exclusively detectable on T  cells of  homozygous B-hCD3EDG/hCDH17 mice but not in wild-type mice.

Western blot analysis of CDH17 protein expression in homozygous B-hCD3EDG/hCDH17 mice. Colon and small intestine tissue lysates were collected from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hCD3EDG/hCDH17 mice (H/H;H/H), and then analyzed by western blot with species-specific anti-human CDH17(abcam, ab109190) and anti-mouse CDH17 (R&D, AF8524) antibodys. 40 μg total proteins were loaded for western blotting analysis. CDH17 was detected in colon and small intestine.