The use of the Dhcr7 knockout mouse to accurately determine the origin of fetal sterols. J Lipid Res 2006 Jul;47(7):1535-41
Date
05/03/2006Pubmed ID
16651660Pubmed Central ID
PMC1488821DOI
10.1194/jlr.M600141-JLR200Scopus ID
2-s2.0-33746095457 (requires institutional sign-in at Scopus site) 88 CitationsAbstract
Mice with a targeted mutation of 3beta-hydroxysterol Delta(7)-reductase (Dhcr7) that cannot convert 7-dehydrocholesterol to cholesterol were used to identify the origin of fetal sterols. Because their heterozygous mothers synthesize cholesterol normally, virtually all sterols found in a Dhcr7 knockout fetus having a Delta(7) or a Delta(8) double bond must have been synthesized by the fetus itself but any cholesterol had to have come from the mother. Early in gestation, most fetal sterols were of maternal origin, but at approximately E13-14, in situ synthesis became increasingly important, and by birth, 55-60% of liver and lung sterols had been made by the fetus. In contrast, at E10-11, upon formation of the blood-brain barrier, the brain rapidly became the source of almost all of its own sterols (90% at birth). New, rapid, de novo sterol synthesis in brain was confirmed by the observation that concentrations of C24,25-unsaturated sterols were low in the brains of all very young fetuses but increased rapidly beginning at approximately E11-12. Reduced activity of sterol C24,25-reductase (Dhcr24) in brain, suggested by the abundance of C24,25-unsaturated compounds, seems to be the result of suppressed Dhcr24 expression. The early fetal brain also appears to conserve cholesterol by keeping cholesterol 24-hydroxylase expression low until approximately E18.
Author List
Tint GS, Yu H, Shang Q, Xu G, Patel SBAuthor
Hongwei Yu MD Professor in the Anesthesiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBase Sequence
Brain
Cholesterol
DNA
Female
Fetus
Liver
Lung
Maternal-Fetal Exchange
Mice
Mice, Knockout
Oxidoreductases Acting on CH-CH Group Donors
Pregnancy
Sterols
