Cholesterol Precursors Can Cause Developmental Defects

Main Category: Cholesterol
Also Included In: Pregnancy / Obstetrics;  Cleft Palate
Article Date: 05 Sep 2006 - 20:00 PDT

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Although high levels of cholesterol are bad for us (putting us at increased risk of a heart attack), low levels of cholesterol can also be bad -- as a fetus, low levels of cholesterol are associated with life-long disabilities, such as learning difficulties, limb abnormalities, and cleft palate. Low levels of cholesterol during development are caused by genetic defects in the proteins that control the production of cholesterol. Therefore, these individuals not only have low levels of cholesterol but also high levels of cholesterol precursors; which of these cause the developmental defects has been a matter of debate. Now, researchers from the University of Texas Southwestern Medical Center have shown that in mice it is the high levels of cholesterol precursors that are to blame.

In their study, which appears in the September issue of the Journal of Clinical Investigation, Joseph Goldstein and colleagues found that fetal mice with normal levels of cholesterol but very high levels of cholesterol precursors had severe developmental defects, including cleft palate. Treating female mice during pregnancy with a statin (a drug that decreases the production of cholesterol) reduced the level of cholesterol precursors in the fetal mice and decreased the incidence of cleft palate. This study provides enormous insight into why certain gene defects cause disability.

In an accompanying commentary, Forbes Porter from the National Institutes of Health puts this work in context with other recent advances and outlines the work that remains before we can fully understand how high levels of cholesterol precursors cause disabilities.

TITLE: Severe facial clefting in Insig-deficient mouse embryos caused by sterol accumulation and reversed by lovaststin

AUTHOR CONTACT:

Joseph L. Goldstein
University of Texas Southwestern Medical Center, Dallas, Texas, USA.
E-mail: joe.goldstein@utsouthwestern.edu.

Michael S. Brown
University of Texas Southwestern Medical Center, Dallas, Texas, USA.
E-mail: mike.brown@utsouthwestern.edu.

View the PDF of this article at: https://www.the-jci.org/article.php?id=28988

ACCOMPANYING COMMENTARY

TITLE: Cholesterol precursors and facial clefting

AUTHOR CONTACT:

Forbes D. Porter
National Institutes of Health, Bethesda, Maryland, USA.
E-mail: fdporter@mail.nih.gov.

View the PDF of this article at: https://www.the-jci.org/article.php?id=29872

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JCI table of contents: September 1, 2006

Contact: Karen Honey
Journal of Clinical Investigation

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