Cytokeratins 8 and 19 in the mouse placental development

To investigate the expression and biological roles of cytokeratin 19 (K19) in development and in adult tissues, we inactivated the mouse K19 gene (Krt 1-19) by inserting a bacterial beta -galactosidase gene (lacZ) by homologou s recombination in embryonic stem cells, and established germ line mutant m ice. Both heterozygous and homozygous mutant mice were viable, fertile, and appeared normal. By 7.5-8.0 days post coitum (dpc), heterozygous mutant em bryos expressed lacZ in the notochordal plate and hindgut diverticulum, ref lecting the fact that the notochord and the gut endoderm are derived from t he axial mesoderm-originated cells. In the adult mutant, lacZ was expressed mainly in epithelial tissues. To investigate the possible functional coope ration and synergy between K19 and K8, we then constructed compound homozyg ous mutants, whose embryos died similar to 10 dpc. The lethality resulted f rom defects in the placenta where both K19 and K8 are normally expressed. A s early as 9.5 dpc, the compound mutant placenta had an excessive number of giant trophoblasts, but lacked proper labyrinthine trophoblast or spongiot rophoblast development, which apparently caused flooding of the maternal bl ood into the embryonic placenta. These results indicate that K19 and K8 coo perate in ensuring the normal development of placental tissues.