Basic Information
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Description
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- GIPR, gastric Inhibitory polypeptide receptor, belongs to 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 diabetes1,2.
- Biocytogen developed a GIPR humanized mice, the full coding sequences of human GIPR gene plus 3’UTR was inserted into the mouse Gipr in-situ. Then, confirmed that human GIPR mRNA was detectable only in homozygous B-hGIPR mice but not in wild-type mice. GIPR protein was detected in brain, stomach, pancreas and liver of homozygous B-hGIPR mice. During the IGPTT, human GIP induced the plasma insulin secretion and inhibit the glucose secretion.
- The mice can be used for preclinical pharmacodynamics studies of target-related disease.
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Targeting strategy
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Gene targeting strategy for B-hGIPR mice. The full coding region sequences of 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.
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mRNA expression analysis
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Strain specific analysis of GIPR mRNA expression in wild-type C57BL/6 mice and B-hGIPR mice by RT-PCR. Brain, eWAT and ingWAT RNA were isolated from wild-type C57BL/6 mice (+/+) and homozygous B-hGIPR mice (H/H), then cDNA libraries were synthesized by reverse transcription, followed by PCR with mouse or human GIPR primers. Mouse Gipr mRNA was detectable only in wild-type C57BL/6 mice. Human GIPR mRNA was detectable only in homozygous B-hGIPR mice but not in wild-type mice. eWAT, epididymal white adipose tissue; ingWAT, inguinal white adipose tissue.
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GIPR expression analysis by WB
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Western blot analysis of GIPR protein expression in homozygous B-hGIPR mice. Various tissue lysates were collected from wild-type C57BL/6N mice (+/+) and homozygous B-hGIPR mice (H/H), and then analyzed by western blot with anti-GIPR antibody. 40 μg total proteins were loaded for western blotting analysis. GIPR was detected in brain, stomach, pancreas and liver.
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GIPR expression analysis by IHC
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Representative GIPR expression in different tissues of B-hGIPR mice by IHC. Tissues were stained with antibodies that recognized with both human and mouse GIPR (B-J) or anti-IgG antibody (A). Pancreas and brain of B-hGIPR mice and wild-type C57BL/6 mice show GIPR positive. Liver and adipose of B-hGIPR mice and wild-type C57BL/6 mice show GIPR negative. Mouse tissues from the wild-type C57BL/6 mice (A-E). Human pancreas carcinoma as a positive control (F). Other tissues were got from homozygous B-hGIPR mice (G-J). Original magnification ×200. Abbreviations: IHC, immunohistochemistry.
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In vivo function of exogenous GIP during IGPTT
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In vivo function of m/hGIP during IGPTT
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In vivo function of m/hGIP during IGPTT. Plasma glucose and insulin concentrations were measured after intraperitoneal injection of 50 nmol/kg mouse GIP (Cat. HY-P77948, MCE) or human GIP (Cat. HY-P0276, MCE) and glucose (40%) in wild-type C57BL/6J mice and B-hGIPR mice. (male, 6-week-old, n=6). Data represent means ± SEM. Analyzed by 2way-ANOVA,*P<0.05, **P<0.01, ***P<0.001
