hMRGPRX2

Fig.1 Detection of MRGPRX2 expression in bladder by RT-PCR. 

Wild type: only one band at 265 bp with primers F1/R1 (mMrgprb2);

Homozygous: only one band at 383 bp with primers F2/R2 (hMRGPRX2).

Abbr. M, DNA marker; HO, homozygous; WT, wild type.

Fig.2 Characterization of MRGPRX2 (X2) Expression. huX2 immunoreactivity was observed in flow isolated peritoneal mast cells (PMCs) from X2-KI but not WT control mice or staining controls (isotype CTR). (Data from a collaborator)

Fig.3 MRGPRX2 is not expressed on macrophages (as expected).  (Data from a collaborator)

Fig.4  Evans blue extravasation assays of Cortistatin-14 and Substance P induced WT C57BL/6 mice and HO hMRGPRX2 mice.

The dorsal skin and right ears of WT C57BL/6 mice (8 weeks old,male) and HO hMRGPRX2 mice (8 weeks old, male) were stimulated with Cortistatin-14 and Substance P, respectively, while the left ears were treated with an equal amount of saline as a control. Evans blue extravasation assays revealed that, consistent with literature reports indicating that related stimulants exhibit stronger agonist effects on X2 compared to the murine B2 receptor, hMRGPRX2 mice exhibited significantly higher Evans blue extravasation than WT mice. Furthermore, the extent of extravasation increased in a dose-dependent manner with rising concentrations of Cortistatin-14. This suggests that hMRGPRX2 mice are more suitable for preclinical evaluation of related drugs compared to WT mice.

Fig.5 In vivo efficacy study of test durg in HO hMRGPRX2 mice.

Pharmacodynamic evaluation of Compound 1 and Compound 2 (provided by a collaborative partner) on Cortistatin-14-induced vascular leakage in HO hMRGPRX2 mice (8 weeks old, male). Evans blue quantification results showed that both Compound 1 and Compound 2 significantly attenuated MRGPRX2 agonist cortistatin-14-induced vascular leakage in dorsal skin and right ear tissue of hMRGPRX2 mice, indicating that hMRGPRX2 mice exhibit good responsiveness to related drugs.