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Published online 30 October 2000. doi:10.1083/jcb.151.3.563
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© The Rockefeller University Press, 0021-9525/2000//563 $5.00
The Journal of Cell Biology, Volume 151, Number 3, , 2000 563-572

Original Article

Cytokeratins 8 and 19 in the Mouse Placental Development



Yoshitaka Tamaia, Tomo-o Ishikawaa, Michael R. Bösla, Masahiko Morib, Masami Nozakic, Heléne Baribaultd, Robert G. Oshimad, and Makoto M. Taketoe

a Banyu Tsukuba Research Institute (Merck), Tsukuba, Ibaraki 300-2611, Japan
b National Institute of Radiological Sciences, Inage-ku, Chiba 263-8555, Japan
c Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan
d The Burnham Institute, La Jolla, California 92037
e Graduate School of Pharmaceutical Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan
Laboratory of Biomedical Genetics, Graduate School of Pharmaceutical Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.81-3-5841-477881-3-5841-4859

To investigate the expression and biological roles of cytokeratin 19 (K19) in development and in adult tissues, we inactivated the mouse K19 gene (Krt1-19) by inserting a bacterial β-galactosidase gene (lacZ) by homologous recombination in embryonic stem cells, and established germ line mutant mice. Both heterozygous and homozygous mutant mice were viable, fertile, and appeared normal. By 7.5–8.0 days post coitum (dpc), heterozygous mutant embryos expressed lacZ in the notochordal plate and hindgut diverticulum, reflecting the fact that the notochord and the gut endoderm are derived from the axial mesoderm-originated cells. In the adult mutant, lacZ was expressed mainly in epithelial tissues. To investigate the possible functional cooperation and synergy between K19 and K8, we then constructed compound homozygous mutants, whose embryos died ~10 dpc. The lethality resulted from defects in the placenta where both K19 and K8 are normally expressed. As early as 9.5 dpc, the compound mutant placenta had an excessive number of giant trophoblasts, but lacked proper labyrinthine trophoblast or spongiotrophoblast development, which apparently caused flooding of the maternal blood into the embryonic placenta. These results indicate that K19 and K8 cooperate in ensuring the normal development of placental tissues.

Key Words: embryo • endoderm • epithelium • keratin • trophoblasts

© 2000 The Rockefeller University Press

Dr. Ishikawa's present address is Department of Pharmacology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. Dr. Bösl's present address is Zentrum für Molekulare Neurobiologie, Universität Hamburg, Hamburg, D-20246, FRG. Dr. Baribault's present address is Deltagen Inc., San Carlos, CA 94061.

Abbreviations used in this paper: dpc, days post coitum; ES, embryonic stem; K, cytokeratin.


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