Severe atherosclerosis and hypoalphalipoproteinemia in the staggerer mouse, a mutant of the nuclear receptor ROR(alpha)

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, d...

Full description

Saved in:
Bibliographic Details
Published in:Circulation (New York, N.Y.) N.Y.), 1998-12, Vol.98 (24), p.2738
Main Authors: Mamontova, Anna, Seguret-Mace, Sandrine, Esposito, Bruno, Chaniale, Colette
Format: Article
Language:English
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
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 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.
ISSN:0009-7322
1524-4539