(Circulation. 1998;98:2738-2743.)
© 1998 American Heart Association, Inc.
Basic Science Reports |
Severe Atherosclerosis and Hypoalphalipoproteinemia in the Staggerer Mouse, a Mutant of the Nuclear Receptor ROR
From INSERM U141 and IFR "Circulation Lariboisière," Paris (A.M., B.E., A.T.); Rhône-Poulenc Rorer, Gencell Division, Atherosclerosis Department, Centre de recherches de Vitry-Alfortville, Vitry sur Seine (S.S.-M., N.D.); Institut Gustave Roussy, Villejuif (C.C.); INSERM U325, Département d'Athérosclérose, Institut Pasteur, Lille (M.B., G.L., B.S.); and Laboratoire de Neurobiologie du Développement, Institut des Neurosciences, CNRS URA1488 and Université P. et M. Curie, Paris (N.D.-B., J.M.), France.
Correspondence to Alain Tedgui, INSERM U141, 41 Blvd de la Chapelle, 75475 Paris Cedex 10, France.
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 ROR 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 ROR gene
contributes to the plasma HDL level and susceptibility to
atherosclerosis.
Key Words: hypercholesterolemia • genes • cholesterol • apolipoproteins
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