Skip Navigation


Human Molecular Genetics Advance Access originally published online on September 5, 2008
Human Molecular Genetics 2008 17(23):3806-3813; doi:10.1093/hmg/ddn278
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
17/23/3806    most recent
ddn278v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Lindegaard, M. L.
Right arrow Articles by Porter, F. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lindegaard, M. L.
Right arrow Articles by Porter, F. D.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Published by Oxford University Press 2008

Characterization of placental cholesterol transport: ABCA1 is a potential target for in utero therapy of Smith–Lemli–Opitz syndrome

Marie L. Lindegaard1,*, Christopher A. Wassif1, Boris Vaisman2, Marcelo Amar2, Elizabeth V. Wasmuth1, Robert Shamburek2, Lars B. Nielsen3,4, Alan T. Remaley2 and Forbes D. Porter1

1 Section on Molecular Dysmorphology, Program in Developmental Endocrinology and Genetics, Eunice Kennedy Schriver National Institute of Child Health and Human Development 2 Lipoprotein Metabolism Section, Pulmonary and Vascular Medicine Branch, National Heart, Lung and Blood Institute, NIH, DHHS, Bethesda, MD, USA 3 Department of Clinical Biochemistry, Rigshospitalet 4 Department of Biomedical Sciences, University of Copenhagen, Denmark

* To whom correspondence should be addressed at: Department of Clinical Biochemistry, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark. Tel: +45 35452957; Fax: +45 35452524; Email: marie.s.lindegaard{at}dadlnet.dk

Received July 11, 2008; Revised August 15, 2008; Accepted September 1, 2008

Patients with Smith–Lemli–Opitz syndrome (SLOS) are born with multiple congenital abnormalities. Postnatal cholesterol supplementation is provided; however, it cannot correct developmental malformations due to in utero cholesterol deficit. Increased transport of cholesterol from maternal to fetal circulation might attenuate congenital malformations. The cholesterol transporters Abca1, Abcg1, and Sr-b1 are present in placenta; however, their potential role in placental transport remains undetermined. In mice, expression analyses showed that Abca1 and Abcg1 transcripts increased 2–3-fold between embryonic days 13.5 and 18.5 in placental tissue; whereas, Sr-b1 expression decreased. To examine the functional role of Abca1, Abcg1 and Sr-b1 we measured the maternal–fetal transfer of 14C-cholesterol in corresponding mutant embryos. Disruption of either Abca1 or Sr-b1 decreased cholesterol transfer by ~30%. In contrast, disruption of the Abcg1 had no effect. Treatment of pregnant C57Bl/6 female mice with TO901317, an LXR-agonist, increased both Abca1 expression and maternal–fetal cholesterol transfer to the fetus. In an SLOS mouse model (Dhcr7–/–), which is incapable of de novo synthesis of cholesterol, in utero treatment with TO901317 resulted in increased cholesterol content in Dhcr7–/– embryos. Our data support the hypothesis that Abca1, and possibly Sr-b1, contributes to transport maternal cholesterol to the developing fetus. Furthermore, we show, as a proof of principle, that modulating maternal–fetal cholesterol transport has potential for in utero therapy of SLOS.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Lipid Res.Home page
K. T. Burke, P. L. Colvin, L. Myatt, G. A. Graf, F. Schroeder, and L. A. Woollett
Transport of maternal cholesterol to the fetus is affected by maternal plasma cholesterol concentrations in the Golden Syrian hamster
J. Lipid Res., June 1, 2009; 50(6): 1146 - 1155.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.