• GIPR, gastric Inhibitory polypeptide receptor, belongs to the G-protein coupled receptor family. GIPR is expressed in many tissues including pancreas, stomach, brain, liver, etc. This protein plays a crucial role in regulating insulin secretion, glucose, and lipid metabolism. Mutations or changes within this gene have been associated with various health conditions including obesity and diabetes.
• GLP1R, glucagon-like peptide-1 receptor, G protein-coupled receptor, 7 transmembrane proteins, human-mouse homology 91.79%. Widely distributed in multiple organs or tissues of the body, including the central nervous system, gastrointestinal tract, cardiovascular system, pancreas, liver, adipose tissue, muscle, etc.
• Glucagon acts through a 7-transmembrane class II receptor coupled to G proteins of either Gsα type or Gq type. Receptor activation of Gsα activates adenylate cyclase, resulting in cyclic adenosine monophosphate (cAMP) accumulation and increased protein kinase A activity and activation of the Gq receptor leads to an increase in intracellular Ca2+ through activation of phospholipase C.
• B-hGCGR/hGIPR/hGLP1R plus mice were obtained by mating B-hGCGR mice (110105), B-hGIPR mice (112714), and B-hGLP1R mice plus (113033). For validation data of this mouse model, you can refer to the validation data from the related gene humanized mouse models.

• B-hGCGR/hGIPR/hGLP1R plus mice were obtained by mating B-hGCGR mice (110105), B-hGIPR mice (112714), and B-hGLP1R mice plus (113033). For validation data of this mouse model, you can refer to the validation data from the related gene humanized mouse models.
• Gene targeting strategy for B-hGCGR mice. The exons 2-14 of the mouse Gcgr gene that encode the full-length protein were replaced by human GCGR exons 2-14 in B-hGCGR mice.
• Gene targeting strategy for B-hGIPR mice. The full coding region sequences of the mouse Gipr gene were replaced by human GIPR CDS + 3’UTR in B-hGIPR mice. As a result, mouse Gipr sequences will be deleted, and only human GIPR will be expressed in B-hGIPR mice.
• Gene targeting strategy for B-hGLP1R mice plus. The exon 1 and part of intron 1 of the mouse Glp1r gene were replaced by the human CDS of GLP1R, containing the human intron 2. The chimeric GLP1R expression was driven by the endogenous mouse Glp1r promoter, while the mouse Glp1r gene will be disrupted

Effect of Semaglutide, Tirzepatide, and Retatrutide food intake in B-hGCGR/hGIPR/hGLP1R plus mice. B-hGCGR/hGIPR/hGLP1R plus mice (8 weeks old) were grouped by body weight and daily food intake. All animals will be placed in clean cages and fasted overnight, mice will be dosed with PBS or test compound in the morning (before 10 AM). All group's food will be added 15 minutes post-dosing, and food remaining will be recorded at 2-, 4-, 6-, 8-, and 24 hours post-dosing. Values are expressed as mean ± SEM. Significance was determined by the 2 way ANOVA. (*P <​ 0.05, **P <​ 0.01, ***P <​ 0.001, ****P <​ 0.0001).