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.