Influence of the genetic background on the diabetic phenotype and postnatal development of the endocrine pancreas of GIPRdn transgenic mice

Aims: GIPR^dn transgenic mice on the CD1 outbred genetic background show loss of functional beta cell mass in combination with a severe diabetic phenotype. In this study, the influence of the genetic background FVB/N (F.CD1-GIPR ^dn) and C57Bl/6J (B6.CD1-GIPR ^dn) on the diabetic phenotype and the postnatal development of the endocrine pancreas of GIPR^dn transgenic mice were investigated.

Methods: GIPR^dn transgenic mice were back crossed to FVB/N and C57Bl/6 genetic background for over ten generations. In vivo tests concerning glucose homeostasis and quantitative stereological analyses of the endocrine pancreas were performed.

Results: GIPR^dn transgenic mice on FVB/N background developed severe hyperglycemia, insulin resistance, polydipsia, polyuria and polyphagia as well as significantly lower total islet volumes, total beta cell volumes and total volumes of isolated beta cell as compared to non-transgenic littermates. In contrast, B6.CD1-GIPR ^dn-mice showed a milder diabetic phenotype and a less severe disturbance of pancreatic islet and beta cell development as compared to F.CD1-GIPR ^dn mice. The higher total volume of isolated beta cells could be responsible for the higher total beta cell volume and the milder diabetic phenotype of B6.CD1-GIPR ^dn compared to F.CD1-GIPR ^dn.

Conclusion: Due to the stronger diabetic phenotype, GIPR^dn transgenic mice on the CD1 and FVB/N genetic backgrounds are more appropriate mouse models for studying consequences of severe diabetes, whereas B6.CD1-GIPR ^dn-mice are applicable mouse models for investigating consequence of mild diabetes. We could show that the diabetic phenotype of mice expressing a mutated GIPR^dn is dependent on the genetic background.