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

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 RORα gene, d...

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Published in:Circulation (New York, N.Y.) N.Y.), 1998-12, Vol.98 (24), p.2738-2743
Main Authors: MAMONTOVA, A, SEGURET-MACE, S, TEDGUI, A, ESPOSITO, B, CHANIALE, C, BOULY, M, DELHAYE-BOUCHAUD, N, LUC, G, STAELS, B, DUVERGER, N, MARIANI, J
Format: Article
Language:English
Subjects:
Atherosclerosis (general aspects, experimental research)
Biological and medical sciences
Blood and lymphatic vessels
Cardiology. Vascular system
Medical sciences
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Summary: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 RORα 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 RORα gene contributes to the plasma HDL level and susceptibility to atherosclerosis.
ISSN:0009-7322
1524-4539
DOI:10.1161/01.CIR.98.24.2738