Embryonic Lethality and Defective Neural Tube Closure in Mice Lacking Squalene Synthase*

@article{Tozawa1999EmbryonicLA,
  title={Embryonic Lethality and Defective Neural Tube Closure in Mice Lacking Squalene Synthase*},
  author={Ryu-ichi Tozawa and Shu Ishibashi and Jun-ichi Osuga and Hiroaki Yagyu and Teruaki Oka and Zhong Chen and Ken Ohashi and St{\'e}phane Perrey and Futoshi Shionoiri and Naoya Yahagi and Kenji Harada and Takanari Gotoda and Yoshio Yazaki and Nobuhiro Yamada},
  journal={The Journal of Biological Chemistry},
  year={1999},
  volume={274},
  pages={30843 - 30848}
}
  • Ryu-ichi TozawaShu Ishibashi N. Yamada
  • Published 22 October 1999
  • Biology
  • The Journal of Biological Chemistry
Squalene synthase (SS) catalyzes the reductive head-to-head condensation of two molecules of farnesyl diphosphate to form squalene, the first specific intermediate in the cholesterol biosynthetic pathway. We used gene targeting to knock out the mouse SS gene. The mice heterozygous for the mutation (SS+/−) were apparently normal. SS+/− mice showed 60% reduction in the hepatic mRNA levels of SS compared with SS+/+ mice. Consistently, the SS enzymatic activities were reduced by 50% in the liver… 
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Early Embryonic Lethality Caused by Targeted Disruption of the 3-Hydroxy-3-methylglutaryl-CoA Reductase Gene*

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Intestinal Deletion of 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Promotes Expansion of the Resident Stem Cell Compartment

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Structure and regulation of mammalian squalene synthase.

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It is demonstrated that transient upregulation of SS stimulates cholesterol biosynthesis as well as lipoprotein production, providing the first in vivo evidence that SS plays a regulatory role in cholesterol metabolism through modulation of HMG-CoA reductase activity and cholesterol biosynthetic activity.

Squalene synthase: structure and regulation.

Hydroxysteroid (17beta) dehydrogenase 7 activity is essential for fetal de novo cholesterol synthesis and for neuroectodermal survival and cardiovascular differentiation in early mouse embryos.

The data showed that the lack of HSD17B7 results in a blockage in the de novo cholesterol biosynthesis in mouse embryos in vivo, and H SD17BKO embryos die at embryonic day (E) 10.5.
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