Access

You are not currently logged in.

Access your personal account or get JSTOR access through your library or other institution:

login

Log in to your personal account or through your institution.

If You Use a Screen Reader

This content is available through Read Online (Free) program, which relies on page scans. Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.

Function of IRE1 Alpha in the Placenta Is Essential for Placental Development and Embryonic Viability

Takao Lwawaki, Ryoko Akai, Shinya Yamanaka, Kenji Kohno and Joseph Brewer
Proceedings of the National Academy of Sciences of the United States of America
Vol. 106, No. 39 (Sep. 29, 2009), pp. 16657-16662
Stable URL: http://www.jstor.org/stable/40484960
Page Count: 6
  • Read Online (Free)
  • Subscribe ($19.50)
  • Cite this Item
Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Function of IRE1 Alpha in the Placenta Is Essential for Placental Development and Embryonic Viability
Preview not available

Abstract

Inositol requiring enzyme-1 (IRE1), a protein located on the endoplasmic reticulum (ER) membrane, is highly conserved from yeast to humans. This protein is activated during ER stress and induces cellular adaptive responses to the stress. In mice, IRE1α inactivation results in widespread developmental defects, leading to embryonic death after 12.5 days of gestation. However, the cause of this embryonic lethality is not fully understood. Here, by using in vivo imaging analysis and conventional knockout mice, respectively, we showed that IRE1α was activated predominantly in the placenta and that loss of IRE1α led to reduction in vascular endothelial growth factor-A and severe dysfunction of the labyrinth in the placenta, a highly developed tissue of blood vessels. We also used a conditional knockout strategy to demonstrate that IRE1α-deficient embryos supplied with functionally normal placentas can be born alive. Fetal liver hypoplasia thought to be responsible for the embryonic lethality of IRE1α-null mice was virtually absent in rescued IRE1 α-null pups. These findings reveal that IRE1α plays an essential function in extraembryonic tissues and highlight the relationship of physiological ER stress and angiogenesis in the placenta during pregnancy in mammals.

Page Thumbnails

  • Thumbnail: Page 
[16657]
    [16657]
  • Thumbnail: Page 
16658
    16658
  • Thumbnail: Page 
16659
    16659
  • Thumbnail: Page 
16660
    16660
  • Thumbnail: Page 
16661
    16661
  • Thumbnail: Page 
16662
    16662