The intermediate filament protein keratin 8 (K8) is critical for the development of most mouse embryos beyond midgestation. We find that 68% of K8−/− embryos, in a sensitive genetic background, are rescued from placental bleeding and subsequent death by cellular complementation with wild-type tetraploid extraembryonic cells. This indicates that the primary defect responsible for K8−/− lethality is trophoblast giant cell layer failure. Furthermore, the genetic absence of maternal but not paternal TNF doubles the number of viable K8−/− embryos. Finally, we show that K8−/− concepti are more sensitive to a TNF-dependent epithelial apoptosis induced by the administration of concanavalin A (ConA) to pregnant mothers. The ConA-induced failure of the trophoblast giant cell barrier results in hematoma formation between the trophoblast giant cell layer and the embryonic yolk sac in a phenocopy of dying K8-deficient concepti in a sensitive genetic background. We conclude the lethality of K8−/− embryos is due to a TNF-sensitive failure of trophoblast giant cell barrier function. The keratin-dependent protection of trophoblast giant cells from a maternal TNF-dependent apoptotic challenge may be a key function of simple epithelial keratins.
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26 May 2003
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May 27 2003
Keratin 8 protection of placental barrier function
Daniel Jaquemar,
Daniel Jaquemar
1The Burnham Institute, La Jolla, CA 92037
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Sergey Kupriyanov,
Sergey Kupriyanov
3The Scripps Research Institute, La Jolla, CA 92037
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Miriam Wankell,
Miriam Wankell
1The Burnham Institute, La Jolla, CA 92037
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Jacqueline Avis,
Jacqueline Avis
1The Burnham Institute, La Jolla, CA 92037
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Kurt Benirschke,
Kurt Benirschke
2Department of Pathology, University of California San Diego, San Diego, CA 92103
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Hélène Baribault,
Hélène Baribault
4Tularik Inc., South San Francisco, CA 94080
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Robert G. Oshima
Robert G. Oshima
1The Burnham Institute, La Jolla, CA 92037
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Daniel Jaquemar
1The Burnham Institute, La Jolla, CA 92037
Sergey Kupriyanov
3The Scripps Research Institute, La Jolla, CA 92037
Miriam Wankell
1The Burnham Institute, La Jolla, CA 92037
Jacqueline Avis
1The Burnham Institute, La Jolla, CA 92037
Kurt Benirschke
2Department of Pathology, University of California San Diego, San Diego, CA 92103
Hélène Baribault
4Tularik Inc., South San Francisco, CA 94080
Robert G. Oshima
1The Burnham Institute, La Jolla, CA 92037
Address correspondence to Robert G. Oshima, The Burnham Institute, 10901 North Torrey Pines Rd., La Jolla, CA 92037. Tel.: (858) 646-3147. Fax: (858) 713-6268. E-mail: [email protected]
*
Abbreviations used in this paper: B6;129, C57bL/6;129X1/SvJ; ConA, concanavalin A; E, embryonic day; K8, mouse keratin 8 or endoA; K18, mouse keratin 18 or endoB; TNFR, TNF receptor.
Received:
October 04 2002
Revision Received:
April 08 2003
Accepted:
April 08 2003
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2003
J Cell Biol (2003) 161 (4): 749–756.
Article history
Received:
October 04 2002
Revision Received:
April 08 2003
Accepted:
April 08 2003
Citation
Daniel Jaquemar, Sergey Kupriyanov, Miriam Wankell, Jacqueline Avis, Kurt Benirschke, Hélène Baribault, Robert G. Oshima; Keratin 8 protection of placental barrier function . J Cell Biol 26 May 2003; 161 (4): 749–756. doi: https://doi.org/10.1083/jcb.200210004
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