Keratin 8 protection of placental barrier function

Keratin 8 protection of placental barrier function

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 tetrap...

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Main Authors: Jaquemar, Daniel, Kupriyanov, Sergey, Wankell, Miriam, Avis, Jacqueline, Benirschke, Kurt, Baribault, Hélène, Oshima, Robert G.
Format: Online
Language:English
Published: The Rockefeller University Press 2003
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2199358/
id pubmed-2199358
recordtype oai_dc
spelling pubmed-21993582008-05-01 Keratin 8 protection of placental barrier function Jaquemar, Daniel Kupriyanov, Sergey Wankell, Miriam Avis, Jacqueline Benirschke, Kurt Baribault, Hélène Oshima, Robert G. Article 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. The Rockefeller University Press 2003-05-26 /pmc/articles/PMC2199358/ /pubmed/12771125 http://dx.doi.org/10.1083/jcb.200210004 Text en Copyright © 2003, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Jaquemar, Daniel
Kupriyanov, Sergey
Wankell, Miriam
Avis, Jacqueline
Benirschke, Kurt
Baribault, Hélène
Oshima, Robert G.
spellingShingle Jaquemar, Daniel
Kupriyanov, Sergey
Wankell, Miriam
Avis, Jacqueline
Benirschke, Kurt
Baribault, Hélène
Oshima, Robert G.
Keratin 8 protection of placental barrier function
author_facet Jaquemar, Daniel
Kupriyanov, Sergey
Wankell, Miriam
Avis, Jacqueline
Benirschke, Kurt
Baribault, Hélène
Oshima, Robert G.
author_sort Jaquemar, Daniel
title Keratin 8 protection of placental barrier function
title_short Keratin 8 protection of placental barrier function
title_full Keratin 8 protection of placental barrier function
title_fullStr Keratin 8 protection of placental barrier function
title_full_unstemmed Keratin 8 protection of placental barrier function
title_sort keratin 8 protection of placental barrier function
description 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.
publisher The Rockefeller University Press
publishDate 2003
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2199358/
_version_ 1611432938499473408

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