Summary: | 碩士 === 國立陽明大學 === 生命科學暨基因體科學研究所 === 95 === The Wnt signaling pathway plays an important role to regulate cell proliferation, tissue differentiation and organogenesis during mammalian development. Beta-catenin is the effector of the Wnt signaling pathway. Previous evidences suggest that the Wnt/beta-catenin signaling is involved in the regulation of liver development, regeneration and pathogenesis. To study the physiological role of beta-catenin in the development of mouse liver, we generated hepatocyte-specific beta-catenin knockout in the fetal liver by crossing Afp-Cre transgenics with mice containing conditional beta-catenin allele (Ctnnb1flx/flx). Our data indicated that about 72% of the hepatocyte-specific beta-catenin knockout (Afp-Cre;Ctnnb1flx/flx) newborns died immediately after birth; about 33% of the newborns died before postnatal day 3; only about 18% of the mice survived to weaning and adulthood. Immunohistochemical staining demonstrated that beta-catenin expression was lost in most of the hepatocytes of fetal liver of the Afp-Cre;Ctnnb1flx/flx mice. Decreased protein expression of the beta-catenin target genes, E-cadherin and glutamine synthetase, was detected in the livers of E18.5embryo and P0 newborns of the Afp-Cre;Ctnnb1flx/flx mice. Dramatic decrease of mRNA expression of the beta-catenin target genes, Cyp2e1 and Cyp1a2 which are associated with liver metabolism, was also detected by RT-PCR in the knockout livers. Taken together, our data indicated that changes in the expression profile of the beta-catenin target genes in the fetal livers may lead to failure of liver function and contribute to the perinatal lethality phenotype of the hepatocyte-specific beta-catenin knockout mice.
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