Gprasp1-flox Mouse

Gprasp1, also known as G-protein-coupled receptor-associated sorting protein 1, belongs to the GPRASP/ARMCX protein family. It plays a crucial role in the post-endocytic sorting of G-protein-coupled receptors (GPCRs) by binding to trafficking proteins like Beclin2 and the Dysbindin-HRS-Gαs complex [2]. It is also involved in adaptive responses related to chronic treatments with GPCR agonists [2].

Endothelial Gprasp1 knockout mice have a high probability of cerebral hemorrhage, arteriovenous malformations (AVMs), and exhibit vascular anomalies in multiple organs. Gprasp1 loss-of-function causes endothelial dysfunction in vitro and in vivo, activating GPR4/cAMP/MAPK signalling to disturb endothelial functions [1].

In addition, Gprasp1-and Gprasp2-deficient B-cells accumulate in the germinal center, leading to transcriptional abnormalities, excessive somatic hypermutation, and eventually developing a B-cell hyperproliferative disease. Also, silencing of Gprasp1 increases the survival, quiescence, migration, niche retention, and hematopoietic repopulating activity of hematopoietic stem and progenitor cells post-transplant [3,4].

In conclusion, Gprasp1 is essential for maintaining normal endothelial function, B-cell maturation, and hematopoietic stem cell transplantation. The gene knockout mouse models have revealed its key roles in AVMs and lymphoproliferative diseases, providing insights into the underlying disease mechanisms and potential therapeutic targets.