Placentation defects are highly prevalent in embryonic lethal mouse mutants

Vicente Perez-Garcia, Elena Fineberg, Robert Wilson, Alexander Murray, Cecilia Icoresi Mazzeo, Catherine Tudor, Arnold Sienerth, Jacqueline K. White, Elizabeth Tuck, Edward J. Ryder, Diane Gleeson, Emma Siragher, Hannah Wardle-Jones, Nicole Staudt, Neha Wali, John Collins, Stefan Geyer, Elisabeth M. Busch-Nentwich, Antonella Galli, James C. Smith, Elizabeth Robertson, David J. Adams, Wolfgang J. Weninger, Timothy Mohun and Myriam Hemberger ()
Additional contact information
Vicente Perez-Garcia: The Babraham Institute, Babraham Research Campus
Elena Fineberg: The Babraham Institute, Babraham Research Campus
Robert Wilson: The Francis Crick Institute
Alexander Murray: The Babraham Institute, Babraham Research Campus
Cecilia Icoresi Mazzeo: Wellcome Trust Sanger Institute
Catherine Tudor: Wellcome Trust Sanger Institute
Arnold Sienerth: The Babraham Institute, Babraham Research Campus
Jacqueline K. White: Wellcome Trust Sanger Institute
Elizabeth Tuck: Wellcome Trust Sanger Institute
Edward J. Ryder: Wellcome Trust Sanger Institute
Diane Gleeson: Wellcome Trust Sanger Institute
Emma Siragher: Wellcome Trust Sanger Institute
Hannah Wardle-Jones: Wellcome Trust Sanger Institute
Nicole Staudt: Wellcome Trust Sanger Institute
Neha Wali: Wellcome Trust Sanger Institute
John Collins: Wellcome Trust Sanger Institute
Stefan Geyer: Center for Anatomy & Cell Biology, Medical University of Vienna
Elisabeth M. Busch-Nentwich: Wellcome Trust Sanger Institute
Antonella Galli: Wellcome Trust Sanger Institute
James C. Smith: The Francis Crick Institute
Elizabeth Robertson: Sir William Dunn School of Pathology, University of Oxford
David J. Adams: Wellcome Trust Sanger Institute
Wolfgang J. Weninger: Center for Anatomy & Cell Biology, Medical University of Vienna
Timothy Mohun: The Francis Crick Institute
Myriam Hemberger: The Babraham Institute, Babraham Research Campus

Nature, 2018, vol. 555, issue 7697, 463-468

Abstract: Abstract Large-scale phenotyping efforts have demonstrated that approximately 25–30% of mouse gene knockouts cause intrauterine lethality. Analysis of these mutants has largely focused on the embryo and not the placenta, despite the crucial role of this extraembryonic organ for developmental progression. Here we screened 103 embryonic lethal and sub-viable mouse knockout lines from the Deciphering the Mechanisms of Developmental Disorders program for placental phenotypes. We found that 68% of knockout lines that are lethal at or after mid-gestation exhibited placental dysmorphologies. Early lethality (embryonic days 9.5–14.5) is almost always associated with severe placental malformations. Placental defects correlate strongly with abnormal brain, heart and vascular development. Analysis of mutant trophoblast stem cells and conditional knockouts suggests that a considerable number of factors that cause embryonic lethality when ablated have primary gene function in trophoblast cells. Our data highlight the hugely under-appreciated importance of placental defects in contributing to abnormal embryo development and suggest key molecular nodes that govern placenta formation.

Date: 2018
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DOI: 10.1038/nature26002

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