ArticleBMC cardiovascular disorders2003
The rat STSL locus: characterization, chromosomal assignment, and genetic variations in sitosterolemic hypertensive rats.
Article in BMC cardiovascular disorders, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 36 citations in OpenAlex.
- Factors Affecting Circulating Phytosterol Levels: Toward an Integrated Understanding of Atherogenicity and Atheroprotection by Dietary and Circulating Phytosterols.Current atherosclerosis reports · 2025Review
- Differential Effects ofGenes · 2023Article
- Genetic Control of Serum Marinobufagenin in the Spontaneously Hypertensive Rat and the Relationship to Blood Pressure.Journal of the American Heart Association · 2017Article
- Sitosterolemia: diagnosis, investigation, and management.Current atherosclerosis reports · 2014Review
- Investigating Sitosterolemia to Understand Lipid Physiology.Clinical lipidology · 2013Article
- ABCG8 Gene Responses to 8 Weeks Treadmill Running With or Without Pistachia atlantica (Baneh) Extraction in Female Rats.International journal of endocrinology and metabolism · 2012Article
- Antioxidant Supplements Improve Profiles of Hepatic Oxysterols and Plasma Lipids in Butter-fed Hamsters.Nutrition and metabolic insights · 2010Article
- Article
- Sterolins ABCG5 and ABCG8: regulators of whole body dietary sterols.Pflugers Archiv : European journal of physiology · 2007Review
- A detailed Hapmap of the Sitosterolemia locus spanning 69 kb; differences between Caucasians and African-Americans.BMC medical genetics · 2006Article
- The missense mutation in Abcg5 gene in spontaneously hypertensive rats (SHR) segregates with phytosterolemia but not hypertension.BMC genetics · 2005Article
- Sitosterolemia--a rare disease. Are elevated plant sterols an additional risk factor?Zeitschrift fur Kardiologie · 2004Review
- A mouse model of sitosterolemia: absence of Abcg8/sterolin-2 results in failure to secrete biliary cholesterol.BMC medicine · 2004Article
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundElevated plant sterol accumulation has been reported in the spontaneously hypertensive rat (SHR), the stroke-prone spontaneously hypertensive rat (SHRSP) and the Wistar-Kyoto (WKY) rat. Additionally, a blood pressure quantitative trait locus (QTL) has been mapped to rat chromosome 6 in a New Zealand genetically hypertensive rat strain (GH rat). ABCG5 and ABCG8 (encoding sterolin-1 and sterolin-2 respectively) have been shown to be responsible for causing sitosterolemia in humans. These genes are organized in a head-to-head configuration at the STSL locus on human chromosome 2p21.
methodsTo investigate whether mutations in Abcg5 or Abcg8 exist in SHR, SHRSP, WKY and GH rats, we initiated a systematic search for the genetic variation in coding and non-coding region of Abcg5 and Abcg8 genes in these strains. We isolated the rat cDNAs for these genes and characterized the genomic structure and tissue expression patterns, using standard molecular biology techniques and FISH for chromosomal assignments.
resultsBoth rat Abcg5 and Abcg8 genes map to chromosome band 6q12. These genes span ~40 kb and contain 13 exons and 12 introns each, in a pattern identical to that of the STSL loci in mouse and man. Both Abcg5 and Abcg8 were expressed only in liver and intestine. Analyses of DNA from SHR, SHRSP, GH, WKY, Wistar, Wistar King A (WKA) and Brown Norway (BN) rat strains revealed a homozygous G to T substitution at nucleotide 1754, resulting in the coding change Gly583Cys in sterolin-1 only in rats that are both sitosterolemic and hypertensive (SHR, SHRSP and WKY).
conclusionsThe rat STSL locus maps to chromosome 6q12. A non-synonymous mutation in Abcg5, Gly583Cys, results in sitosterolemia in rat strains that are also hypertensive (WKY, SHR and SHRSP). Those rat strains that are hypertensive, but not sitosterolemic (e.g. GH rat) do not have mutations in Abcg5 or Abcg8. This mutation allows for expression and apparent apical targeting of Abcg5 protein in the intestine. These rat strains may therefore allow us to study the pathophysiological mechanisms involved in the human disease of sitosterolemia.
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