• F2RL3 is a member of the Protease-activated Receptor (PAR) family of seven transmembrane G protein-coupled receptors that are activated by proteolysis.
• F2RL3 is widely expressed with highest expression levels being found in the lungs, pancreas, thyroid, testis, and small intestine. It is also observed in platelets, megakaryocytes, and leukocytes.
• F2RL3 is coupled to G proteins containing the alpha and alpha12/13 subunits and has been shown to activate the PLC-IP3-Ca2+ and PLC-DAG-PKC signal transduction pathways. F2RL3 plays an essential role in hemostasis and thrombosis. Interestingly, F2RL3 requires PARD3 as a cofactor to achieve optimal Thrombin-induced platelet activation. F2RL3 has also been suggested to be involved in regulation of gastrointestinal motility, modulation of nociceptive responses, and stimulation of epithelial to mesenchymal transition in alveolar epithelial cells.
• F2RL3 was exclusively detectable in both wild-type mice and homozygous B-hF2RL3 mice, as anti-F2RL3 antibody was cross-reactive between human and mouse.
• Mouse F2rl3 mRNA were detectable only in wild-type C57BL/6JNifdc mice. Human F2RL3 mRNA was detectable only in homozygous B-hF2RL3 mice but not in wild-type mice.
• The exons 1~2 of mouse F2rl3 gene that encodes the full-length protein were replaced by human F2RL3 exons 1~2 in B-hF2RL3 mice.
• B-hF2RL3 mice can be used to evaluate the in vivo efficacy and safe evaluation of small molecule drugs targeting F2RL3.​

Gene targeting strategy for B-hF2RL3 mice. Exons 1~2 of the mouse F2rl3 gene that encodes the full-length protein were replaced by human F2RL3 exons 1~2 in B-hF2RL3 mice.

Strain specific analysis of F2RL3 mRNA expression in wild-type C57BL/6JNifdc mice and B-hF2RL3 mice by RT-PCR. Lung RNA were isolated from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hF2RL3 mice (H/H), then cDNA libraries were synthesized by reverse transcription, followed by PCR with mouse or human F2RL3 primers. Mouse F2rl3 mRNA were detectable only in wild-type C57BL/6JNifdc mice. Human F2RL3 mRNA was detectable only in homozygous B-hF2RL3 mice but not in wild-type mice.

Strain specific F2RL3 expression analysis in homozygous B-hF2RL3 mice by flow cytometry. Platelets were collected from the blood in wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hF2RL3 mice (H/H). Megakaryocyte were collected from the bone marrow in wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hF2RL3 mice (H/H). Protein expression was analyzed with anti-human F2RL3 antibody (Alomone labs, APR-034-F) by flow cytometry. F2RL3 was detectable on both wild-type mice and homozygous B-hF2RL3 mice, as anti-F2RL3 antibody was cross-reactive between human and mouse.

Strain specific F2RL3 expression analysis in homozygous B-hF2RL3 mice by flow cytometry. Bone marrow were collected from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hF2RL3 mice (H/H). Protein expression was analyzed with anti-human F2RL3 antibody (Alomone labs, APR-034-F) by flow cytometry. F2RL3 was detectable in both wild-type mice and homozygous B-hF2RL3 mice, as anti-F2RL3 antibody was cross-reactive between human and mouse.

Strain specific F2RL3 expression analysis in homozygous B-hF2RL3 mice by flow cytometry. Bone marrow were collected from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hF2RL3 mice (H/H). Protein expression was analyzed with anti-human F2RL3 antibody (Alomone labs, APR-034-F) by flow cytometry. F2RL3 was detectable in both wild-type mice and homozygous B-hF2RL3 mice, as anti-F2RL3 antibody was cross-reactive between human and mouse.