• The glucagon-like peptide-1 receptor (GLP1R) is a receptor protein found on beta cells of the pancreas and on neurons of the brain. It is involved in the control of blood sugar levels by enhancing insulin secretion.
• Gene targeting strategy for B-hGLP1R rats. Part of exon 2 and exon 3 of rat Glp1r were replaced by the P2A and human CDS of GLP1R. The promoter, 5’UTR,  rat exon 1, and intron 1 were retained. The GLP1R protein expression will be driven by the endogenous rat Glp1r promoter, while rat Glp1r gene transcription and translation will be disrupted.
• Validation: Human GLP1R mRNA was detectable only in homozygous B-hGLP1R rats but not in wild-type SD rats. Human GLP1R protein was detectable only in homozygous B-hGLP1R rats but not in wild-type SD rats. Rat GLP1R was detectable only in wild-type SD rats, but not in homozygous B-hGLP1R rats.
• Application: Applied to the efficacy evaluation and toxicity in the field of obesity.

Gene targeting strategy for B-hGLP1R rats. Part of exon 2 and exon 3 of rat Glp1r were replaced by the P2A and human CDS of GLP1R. The promoter, 5’UTR,  rat exon 1, and intron 1 were retained. The GLP1R protein expression will be driven by the endogenous rat Glp1r promoter, while rat Glp1r gene transcription and translation will be disrupted.

Strain specific analysis of GLP1R mRNA expression in wild-type SD rats and B-hGLP1R rats by RT-PCR. Brain RNA was isolated from wild-type SD rats (+/+) and homozygous B-hGLP1R rats (H/H), then cDNA libraries were synthesized by reverse transcription, followed by PCR with human GLP1R primers. Rat Glp1r mRNA was weakly detectable in wild-type SD rats. Human GLP1R mRNA was detectable only in homozygous B-hGLP1R rats but not in wild-type rats.

Representative human GLP1R expression in different tissues of B-hGLP1R rats by IHC. Tissues were stained with human-specific GLP1R antibody (abcam, ab254352) (A-H). The pancreas of SD rats shows human GLP1R negative (A). Brain, pancreas, lung, small intestine, large intestine, and muscle in homozygous B-hGLP1R rats show human GLP1R positive (B-G). Adipose in homozygous B-hGLP1R rats shows human GLP1R negative (H). Original magnification ×200. Abbreviations: IHC, immunohistochemistry.

Representative rat GLP1R expression in different tissues of B-hGLP1R rats by IHC. Tissues were stained with mouse-specific GLP1R antibody (abcam, ab218532) (A-H). The pancreas of SD rats shows rat GLP1R positive (A). Brain, pancreas, lung, small intestine, adipose, large intestine, and muscle in homozygous B-hGLP1R rats show rat GLP1R negative (B-H). Original magnification ×200. Abbreviations: IHC, immunohistochemistry.