Generation and characterisation of a humanised GLP-1 receptor mouse model for translational drug development.

ABSTRACT:

Background

Injectable peptide-based glucagon-like peptide-1 receptor (GLP1R) agonists (GLP1RAs) are effective treatments for obesity and diabetes but are limited by patient compliance and scalability challenges. In contrast, non-peptide small-molecule GLP1RAs offer the advantage of oral delivery but are relatively inactive at the rodent GLP1R, limiting their utility in preclinical pharmacodynamic studies. This study aimed to bridge the translational gap by engineering and thoroughly validating a humanised GLP-1 receptor (hGLP1R) mouse model that more accurately recapitulates human receptor pharmacology, thereby enhancing its utility for preclinical drug development.

Methods

The hGLP1R mouse was generated via CRISPR-Cas9-mediated replacement of the endogenous murine Glp1r gen

SUBMITTER: Sonne N 

PROVIDER: S-EPMC12855590 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature