B-hGIPR mice

C57BL/6-Giprtm2(GIPR)Bcgen/Bcgen • 112714

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B-hGHRL mice
B-hGIPR/hGCGR mice

B-hGIPR mice

Product nameB-hGIPR mice
Catalog number112714
Strain nameC57BL/6-Giprtm2(GIPR)Bcgen/Bcgen
Strain backgroundC57BL/6
AliasesPGQTL2
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  • Description
  • Targeting strategy
  • Phenotypic analysis

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      Description

      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 diabetes.

      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.

      Targeting strategy

      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.

      mRNA expression analysis
      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.
      GIPR expression analysis by WB
      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.
      GIPR expression analysis by IHC
      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.
      In vivo function of m/hGIP during IGPTT

      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