Targeted deletion of keratins 18 and 19 leads to trophoblast fragility and early embryonic lethality
- PMID: 11013209
- PMCID: PMC302090
- DOI: 10.1093/emboj/19.19.5060
Targeted deletion of keratins 18 and 19 leads to trophoblast fragility and early embryonic lethality
Abstract
It has been reported previously that keratin 8 (K8)-deficient mice of one strain die from a liver defect at around E12.5, while those of another strain suffer from colorectal hyperplasia. These findings have generated considerable confusion about the function of K8, K18 and K19 that are co-expressed in the mouse blastocyst and internal epithelia. To resolve this issue, we produced mice doubly deficient for K18 and K19 leading to complete loss of keratin filaments in early mouse development. These embryos died at around day E9.5 with 100% penetrance. The absence of keratins caused cytolysis restricted to trophoblast giant cells, followed by haematomas in the trophoblast layer. Up to that stage, embryonic development proceeded unaffected in the absence of keratin filaments. K18/19-deficient mouse embryos die earlier than any other intermediate filament knockouts reported so far, suggesting that keratins, in analogy to their well established role in epidermis, are essential for the integrity of a specialized embryonic epithelium. Our data also offer a rationale to explore the involvement of keratin mutations in early abortions during human pregnancies.
Figures
Similar articles
-
Keratins in the human trophoblast.Histol Histopathol. 2013 Jul;28(7):817-25. doi: 10.14670/HH-28.817. Epub 2013 Mar 1. Histol Histopathol. 2013. PMID: 23450430 Review.
-
A mutation of keratin 18 within the coil 1A consensus motif causes widespread keratin aggregation but cell type-restricted lethality in mice.Exp Cell Res. 2007 Aug 15;313(14):3127-40. doi: 10.1016/j.yexcr.2007.05.019. Epub 2007 May 25. Exp Cell Res. 2007. PMID: 17617404
-
Keratin transgenic and knockout mice: functional analysis and validation of disease-causing mutations.Methods Mol Biol. 2007;360:203-51. doi: 10.1385/1-59745-165-7:203. Methods Mol Biol. 2007. PMID: 17172732 Review.
-
Type II keratins precede type I keratins during early embryonic development.Eur J Cell Biol. 2005 Aug;84(8):709-18. doi: 10.1016/j.ejcb.2005.04.001. Eur J Cell Biol. 2005. PMID: 16180309
-
Rescue of keratin 18/19 doubly deficient mice using aggregation with tetraploid embryos.Eur J Cell Biol. 2005 Mar;84(2-3):355-61. doi: 10.1016/j.ejcb.2004.12.014. Eur J Cell Biol. 2005. PMID: 15819413
Cited by
-
How great thou ART: biomechanical properties of oocytes and embryos as indicators of quality in assisted reproductive technologies.Front Cell Dev Biol. 2024 Feb 15;12:1342905. doi: 10.3389/fcell.2024.1342905. eCollection 2024. Front Cell Dev Biol. 2024. PMID: 38425501 Free PMC article. Review.
-
Trophoblast Differentiation: Mechanisms and Implications for Pregnancy Complications.Nutrients. 2023 Aug 12;15(16):3564. doi: 10.3390/nu15163564. Nutrients. 2023. PMID: 37630754 Free PMC article. Review.
-
KRT18 regulates trophoblast cell migration and invasion which are essential for embryo implantation.Reprod Biol Endocrinol. 2023 Aug 24;21(1):78. doi: 10.1186/s12958-023-01129-y. Reprod Biol Endocrinol. 2023. PMID: 37620903 Free PMC article.
-
The long protostomic-type cytoplasmic intermediate filament (cIF) protein in Branchiostoma supports the phylogenetic transition between the protostomic- and the chordate-type cIFs.Protoplasma. 2023 Nov;260(6):1493-1500. doi: 10.1007/s00709-023-01865-3. Epub 2023 May 20. Protoplasma. 2023. PMID: 37209173
-
Highly efficient generation of blastocyst-like structures from spliceosomes-repressed mouse totipotent blastomere-like cells.Sci China Life Sci. 2023 Mar;66(3):423-435. doi: 10.1007/s11427-022-2209-3. Epub 2023 Jan 10. Sci China Life Sci. 2023. PMID: 36633710
References
-
- Bancroft J.D. and Cook,H.C. (1994) Manual of Histological Techniques and their Diagnostic Application. Churchill Livingstone, Edinburgh.
-
- Baribault H., Price,J., Miyai,K. and Oshima,R.G. (1993) Mid-gestational lethality in mice lacking keratin 8. Genes Dev., 7, 1191–1202. - PubMed
-
- Baribault H., Penner,J., Iozzo,R.V. and Wilson,H.M. (1994) Colorectal hyperplasia and inflammation in keratin 8-deficient FVB/N mice. Genes Dev., 8, 2964–2973. - PubMed
-
- Bierkamp C., Mclaughlin,K.J., Schwarz,H., Huber,O. and Kemler,R. (1996) Embryonic heart and skin defects in mice lacking plakoglobin. Dev. Biol., 180, 780–785. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
Research Materials