• MRGPRX4 (MAS Related GPR Family Member X4) is expressed in human dorsal root ganglion (hDRG) neurons and co-expresses with the itch receptor HRH1. As a novel bile acid receptor, MRGPRX4 likely mediates cholestatic itch in humans, presenting a promising new target for the development of anti-itch therapies.
• After the induction by Deoxycholic acid (DCA), increased scratching bouts can be observed in both heterozygous and homozygous B-hMRGPRX4 mice.
• B-hMRGPRX4 mice strain was obtained by mating a mouse with a loxP-flanked STOP cassette that prevents transcription of a CAG promoter-driven human MRGPRX4, all inserted into mouse Hipp11 (H11)locus, with a Mrgpra3 Cre-mediated mouse. B-hMRGPRX4 mice express robust human MRGPRX4 following Cre-mediated recombination.

Gene targeting strategy for B-hMRGPRX4 mice. B-hMRGPRX4 mice strain was obtained by mating a mouse with a loxP-flanked STOP cassette that prevents transcription of a CAG promoter-driven human MRGPRX4, all inserted into mouse Hipp11 (H11)locus, with a Mrgpra3 Cre-mediated mouse. B-hMRGPRX4 mice express robust human MRGPRX4 following Cre-mediated recombination. This strain is congenic on the C57BL/6JNifdc genetic background.

Deoxycholic acid induced scratching. Mice receive Deoxycholic acid (DCA) injection. Scratching bouts over a 30-minute period after DCA injection were recorded (A). After the induction by DCA, increased scratching bouts can be observed in both heterozygous and homozygous B-hMRGPRX4 mice, but not in wild-type C57BL/6JNifdc mice (B). Two-way ANOVA with Sidak‘s test mean±sem, *P < 0.05, **P < 0.01, n=3-5. n.s.-non-significant.