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Circulation. 1998 Dec 15;98(24):2738-43.

Severe atherosclerosis and hypoalphalipoproteinemia in the staggerer mouse, a mutant of the nuclear receptor RORalpha.

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  • 1INSERM U141 and IFR "Circulation Lariboisière," Rhône-Poulenc Rorer, Gencell Division, Atherosclerosis Department, Centre de recherches de Vitry-Alfortville, France.

Abstract

BACKGROUND:

Hypoalphalipoproteinemia is the most common lipoprotein abnormality in patients with coronary artery disease, yet its causes are unknown.

METHODS AND RESULTS:

We show that the homozygous staggerer (sg/sg) mutant mouse, which carries a deletion within the nuclear receptor RORalpha gene, develops severe atherosclerosis when maintained on an atherogenic diet. In addition, sg/sg mice display a profound hypoalphalipoproteinemia, which is associated with decreased plasma levels of the major HDL proteins, apolipoprotein (apo) A-I and apoA-II. This decrease in HDL levels in sg/sg mice is due to lowered apoA-I gene expression in the intestine but not in the liver. ApoA-II gene expression is unaffected.

CONCLUSIONS:

These results suggest that the RORalpha gene contributes to the plasma HDL level and susceptibility to atherosclerosis.

PMID:
9851961
[PubMed - indexed for MEDLINE]
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