A mouse model of sitosterolemia: absence of Abcg8/sterolin-2 results in failure to secrete biliary cholesterol
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BioMed Central
Open Access
Research article
A mouse model of sitosterolemia: absence of Abcg8/sterolin-2 results in failure to secrete biliary cholesterol Eric L Klett*1, Kangmo Lu1, Astrid Kosters2, Edwin Vink2, Mi-Hye Lee1, Michael Altenburg3, Sarah Shefer4, Ashok K Batta5, Hongwei Yu1, Jianliang Chen1, Richard Klein1, Norbert Looije2, Ronald Oude-Elferink2, Albert K Groen2, Nobuyo Maeda3, Gerald Salen4,5 and Shailendra B Patel1 Address: 1Division of Endocrinology, Diabetes and Medical Genetics, Medical University of South Carolina, Charleston, SC 29403, USA, 2Department of Experimental Hepatology, AMC Liver Center, Academic Medical Center, Amsterdam 1105 BK, The Netherlands, 3Department of Pathology, School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA, 4Department of Medicine, UMD-New Jersey Medical School, Newark, NJ 07013, USA and 5Research Service and Medical Service, Department of Veterans Affairs Medical Center, East Orange, NJ 07019, USA Email: Eric L Klett* - [email protected]; Kangmo Lu - [email protected]; Astrid Kosters - [email protected]; Edwin Vink - [email protected]; Mi-Hye Lee - [email protected]; Michael Altenburg - [email protected]; Sarah Shefer - [email protected]; Ashok K Batta - [email protected]; Hongwei Yu - [email protected]; Jianliang Chen - [email protected]; Richard Klein - [email protected]; Norbert Looije - [email protected]; Ronald Oude-Elferink - [email protected]; Albert K Groen - [email protected]; Nobuyo Maeda - [email protected]; Gerald Salen - [email protected]; Shailendra B Patel - [email protected] * Corresponding author
Published: 24 March 2004 BMC Medicine 2004, 2:5
Received: 17 November 2003 Accepted: 24 March 2004
This article is available from: http://www.biomedcentral.com/1741-7015/2/5 © 2004 Klett et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
Abstract Background: Mutations in either of two genes comprising the STSL locus, ATP-binding cassette (ABC)-transporters ABCG5 (encoding sterolin-1) and ABCG8 (encoding sterolin-2), result in sitosterolemia, a rare autosomal recessive disorder of sterol trafficking characterized by increased plasma plant sterol levels. Based upon the genetics of sitosterolemia, ABCG5/sterolin-1 and ABCG8/sterolin-2 are hypothesized to function as obligate heterodimers. No phenotypic difference has yet been described in humans with complete defects in either ABCG5 or ABCG8. These proteins, based upon the defects in humans, are responsible for regulating dietary sterol entry and biliary sterol secretion. Methods: In order to mimic the human disease, we created, by a targeted disruption, a mouse model of sitosterolemia resulting in Abcg8/sterolin-2 deficiency alone. Homozygous knockout mice are viable and exhibit sitosterolemia. Results: Mice deficient in Abcg8 have significantly increased plasma and
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