JCB logo
Keystone Symposia
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 27 May 2003. doi:10.1083/jcb.200210004
This Article
Right arrow Full Text
Right arrow PDF (Full Text)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Jaquemar, D.
Right arrow Articles by Oshima, R. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jaquemar, D.
Right arrow Articles by Oshima, R. G.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
© The Rockefeller University Press, 0021-9525/2003/5/749 $5.00
The Journal of Cell Biology, Volume 161, Number 4, 749-756

Article

 Keratin 8 protection of placental barrier function

Daniel Jaquemar1, Sergey Kupriyanov3, Miriam Wankell1, Jacqueline Avis1, Kurt Benirschke2, Hélène Baribault4 and Robert G. Oshima1

1 The Burnham Institute, La Jolla, CA 92037
2 Department of Pathology, University of California San Diego, San Diego, CA 92103
3 The Scripps Research Institute, La Jolla, CA 92037
4 Tularik Inc., South San Francisco, CA 94080

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: rgoshima{at}burnham.org

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.

Key Words: keratin; placenta; TNF; concanavalin A; intermediate filament

* 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.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents