STOCK Glp1r^em1Aglu/J

Stock number: 040551
Product name: Glp1r^S33W
Research areas: Diabetes and Obesity Research, Metabolism Research, Research Tools

Description

Glp1r^S33W mice carry an S33W mutation in the mouse Glp1r locus, retaining responsiveness to peptide-based GLP1RAs while gaining sensitivity to human-specific small molecule GLP1RAs. These humanized Glp1r^S33W mice may serve as an in vivo model system for investigating GLP1RA class of drugs.

Detailed description

Glucagon-like peptide-1 receptor agonists (GLP1RAs) effectively reduce body weight and improve metabolic outcomes. Glp1r^S33W mice carry an S33W mutation into the mouse glucagon-like peptide 1 receptor (Glp1r) locus, which retains responsiveness to peptide-based GLP1RAs while gaining sensitivity to human-specific small molecule GLP1RAs. Homozygous mice are viable and fertile. They do not exhibit differences in respiratory exchange ratio (RER), energy expenditure (EE), or body weight. These humanized Glp1r^S33W mice may serve as an in vivo model system for investigating the small-molecule GLP1R agonists for effective pharmacological interventions for obesity.

Development

Using CRISPR/Cas9-mediated genome editing, an S33W mutation was introduced the mouse Glp1r locus (reference transcript: ENSMUST00000114574.3). Donor oligo repair template (aagagggtgggagtccagtgggaccagaggggctgctggagccacggggcttctgcttttatttctgctttcccttgtagGGTACCACGGTGTCGCTCTGGGAAACCGTCCAAAAGTGGAGAGAATACCGGCGGCAGTGCCAGCGTTTCCTCACGGAAGCGCCACTCCTGGCCACAGgtgcgtccagatgaggcctcacg), tracrRNA, and Cas9 were microinjected into a fertilized (C57BL/6 x SJL)F1 zygotes which were implanted into a pseudopregnant female. Founder pups were genotyped and backcrossed to C57BL/6J mice for at least 5 generations in the donor laboratory (see SNP note below). Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

In 2025, a 48 SNP (single nucleotide polymorphism) panel analysis, with 43 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the males sent to The Jackson Laboratory Repository. Three of the 43 markers throughout the genome were segregating with SJL and one one marker was segregating with an unknown source. Also, 2 of the 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed genetic background.

Allele

Symbol: Glp1r^em1Aglu
Name: endonuclease-mediated mutation 1, Ali D. Guler
MGI accession ID: MGI:8190292
Generation method: Endonuclease-mediated
Attributes: Humanized sequence
Synonyms: Glp1r^S33W
Marker symbol: Glp1r
Marker name: glucagon-like peptide 1 receptor
Marker synonyms: Glip; GLP-1; GLP-1R; GLP-1-R; GLP1Rc; RATGL1RCP
Chromosome: 17
Strain of origin: (C57BL/6 x SJL)F1
Molecular note: Using CRISPR-Cas9-mediated genome editing, the S33W mutation into the mouse Glp1r locus.