Longevity & AgingHumanised GLP-1 Receptor Mouse Unlocks Oral Weight-Loss Drug Testing
Researchers used CRISPR-Cas9 to replace the mouse GLP-1 receptor gene with its human counterpart, creating a 'humanised' mouse model (hGLP1R). This model was validated using both the injectable peptide drug semaglutide and the oral small-molecule drug orforglipron. Both compounds reduced body weight, food intake, and improved glucose metabolism in hGLP1R mice, while orforglipron had no effect in standard wild-type mice. Brain imaging confirmed overlapping neural activation patterns for both drugs. The model accurately reflects human receptor pharmacology, making it a powerful platform for discovering and testing next-generation oral GLP-1 receptor agonists for obesity and metabolic disease.
