Cited by 95Pregnancy and preeclampsia studiesPeroxisome Proliferator-Activated ReceptorsNuclear Receptors and Signaling

Inactivation of the Nuclear Receptor Coactivator RAP250 in Mice Results in Placental Vascular Dysfunction

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Antonson, Per, Schuster, Gertrud U., Wang, Ling, Rozell, Bjürn, Holter, Elin, Flodby, Per, Treuter, Eckardt, Holmgren, Lars +1 more·2003·Molecular and Cellular Biology

Abstract

Coactivators constitute a diverse group of proteins that are essential for optimal transcriptional activity of nuclear receptors. In the past few years many coactivators have been identified but it is still unclear whether these proteins interact indiscriminately with all nuclear receptors and whether there is some redundancy in their functions. We have previously cloned and characterized RAP250 (ASC-2/PRIP/TRBP/NRC), an LXXLL-containing coactivator for nuclear receptors. In order to study its biological role, Rap250 null mice were generated by gene targeting. Here we show that genetic disruption of Rap250 results in embryonic lethality at embryonic day (E) 13.5. Histological examination of placentas revealed a dramatically reduced spongiotrophoblast layer, a collapse of blood vessels in the region bordering the spongiotrophoblast, and labyrinthine layers in placentas from Rap250(-/-) embryos. These findings suggest that the lethality of Rap250(-/-) embryos is the result of obstructed placental blood circulation. Moreover, the transcriptional activity of PPAR gamma is reduced in fibroblasts derived from Rap250(-/-) embryos, suggesting that RAP250 is an essential coactivator for this nuclear receptor in the placenta. Our results demonstrate that RAP250 is necessary for placental development and thus essential for embryonic development.

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  1. [31]Treuter, E., L. Johansson, J. S. Thomsen, A. Wärnmark, J. Leers, M. Pelto-Huikko, M. Sjöberg, A. P. H. Wright, G. Spyrou, and J.-Å. Gustafsson. 1999. Competition between TRAP220 and TIF2 for binding to nuclear receptors. J. Biol. Chem. 274:6667-6677. [DOI] [PubMed] [Google Scholar]

Cited by

Authors
Antonson, P., Schuster, G. U., Wang, L., Rozell, B., Holter, E., Flodby, P., Treuter, E., Holmgren, L., & Gustafsson, J.-Å.
Affiliations
  • Karolinska Institutet (SE)
  • Department of Medical Nutrition
  • Karolinska University Hospital (SE)
  • Department of Biosciences at Novum, Karolinska Institutet, Novum, S-14157 Huddinge
Corresponding author
Antonson, Per
Venue
Molecular and Cellular Biology
Published
2003-02-01
Volume
23
Issue
4
Pages
1260-1268
ISSN
  • 0270-7306 (ISSN-L)
  • 1098-5549
OpenAlex
W2167985579
Cited by
95
References
45
Citations by year
2026: 1 · 2025: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 3 · 2019: 1 · 2015: 2 · 2014: 5 · 2013: 2 · 2012: 4
FWCI
13.72
Type
journal article
Language
en
Open access
Locations
  • Molecular and Cellular Biology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Svenska Sällskapet för Medicinsk Forskning
  • Magnus Bergvalls Stiftelse
Topics
  • Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
Keywords
nuclear receptor coactivators, LXXLL motif, placental vascular dysfunction, spongiotrophoblast, placental development, embryonic lethality, PPARγ, gene targeting
MeSH terms
Animals, Blood Vessels, Brain, Carrier Proteins, Female, Fetal Death, Embryonic and Fetal Development, Fibroblasts, Genetic Engineering, Heart Defects, Congenital, Placenta, Pregnancy, Transcription Factors, Transcription, Genetic, Receptors, Cytoplasmic and Nuclear, Mice, Knockout, Gene Expression Regulation, Developmental, Intracellular Signaling Peptides and Proteins, Mice, Nuclear Receptor Coactivators

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