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• The MRGPR family is a type of GPCR that is responsible for specifically sensing itch, pain, and inflammation. MRGPRX2 is a receptor expressed on mast cells found in barrier tissues such as the skin, airways, and gastrointestinal tract. It can detect a variety of secretagogues, including polycations and peptides, that trigger the mast cell degranulation response, leading to pseudo-allergic reactions. While itching can prompt scratching behaviors that serve a protective defense function for the body, excessive activation of the receptor can result in the development of various diseases, including allergies and inflammation. Therefore, by blocking the activation of MRGPRX2 and mast cell degranulation, MRGPRX2 antagonists hold potential for the broad treatment of mast cell-mediated diseases.
• The human MRGPRX2 protein was detectable only in mast cells of homozygous humanized mice.

Gene targeting strategy for B-hMRGPRX2 mice plus. The coding region and 3’UTR of mouse Mrgprb2 gene that encode extracellular domain, transmembrane domain and cytoplasmic region are replaced by human MRGPRX2 counterparts in B-hMRGPRX2 mice plus.

MRGPRX2 expression analysis in homozygous B-hMRGPRX2 mice plus by flow cytometry. Peritoneal lavage fluid cells were collected from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hMRGPRX2 mice plus (H/H), and analyzed by flow cytometry with anti-human MRGPRX2 antibody (BioLegend, 359004). hMRGPRX2 was detectable in peritoneal lavage fluid mast cells in homozygous B-hMRGPRX2 mice plus, but not in wild-type mice.