Development of a Hepatocyte-Specific Temporal Genetic Mouse Model Using Albumin Promoter-Driven FlpER2 Expression

Abstract

Tissue-specific gene manipulation using Cre/loxP or Flp/frt recombination systems is a cornerstone of genetically engineered mouse models. In this study, we aim to develop a novel hepatocyte-specific, tamoxifen-inducible Flp mouse line. BAC (bacterial artificial chromosome)-Alb(albumin)-FlpER2(estrogen receptor ligan binding domain) was developed by inserting IRES-FlpER2 cDNA between the translation stop codon and 3′-UTR of the mouse albumin gene in a bacterial artificial chromosome. Upon tamoxifen induction in mice crossed with reporter lines, western blotting, immunohistochemistry, immunofluorescence staining, and X-gal staining (5-bromo-4-chloro-3-indolyl-β-D-galactopyranoside Staining) were used to verify the recombination efficiency and specificity of this mouse model. Recombination was highly efficient and specific in hepatocytes, with no recombination detected in intrahepatic cholangiocytes or other organs in this mouse model. We generated a new tamoxifen-induced hepatocyte-specific mouse model with highly efficient recombination specifically in hepatocytes, and this model can be used to generate tumor model lines.