huGCGR Mouse

The GCGR gene encodes the glucagon receptor, a critical member of the Class B G-protein coupled receptor (GPCR) superfamily. This receptor serves as the primary mediator of glucagon's metabolic actions, predominantly in the liver and kidney, although expression is also noted in the pancreas, heart, and other tissues ^[1]. Glucagon binding to GCGR initiates intracellular signaling cascades primarily through the activation of Gs proteins, stimulating adenylyl cyclase and thereby increasing cyclic AMP (cAMP) levels. This, in turn, activates Protein Kinase A (PKA), leading to the phosphorylation of key enzymes and transcription factors that promote hepatic glucose production via glycogenolysis and gluconeogenesis ^[2-3]. The GCGR-mediated pathway is indispensable for maintaining systemic glucose homeostasis, particularly during fasting or hypoglycemia, acting as a crucial counter-regulatory mechanism to insulin signaling ^[1]. Perturbations in GCGR function, whether through genetic mutations or altered expression, are directly linked to severe metabolic dysregulation, including the pathogenesis of type 2 diabetes and rare syndromes involving pancreatic alpha cell hyperplasia ^[3-4]. Consequently, the glucagon receptor stands out as a pivotal therapeutic target, with pharmacological modulation strategies actively pursued for the treatment of glucose-related metabolic disorders.

The huGCGR mouse is a humanized model constructed by replacing the sequence of the mouse Gcgr gene in situ with the corresponding sequence from the human GCGR gene. The huGCGR mice can be used for studies on obesity, type 2 diabetes, metabolic dysfunction-associated steatohepatitis, and other glucose-related metabolic disorders, as well as for GCGR-targeted drug development.