title: Severe atherosclerosis and hypoalphalipoproteinemia in the staggerer mouse, a mutant of the nuclear receptor RORalpha.
abstract: BACKGROUND
  Hypoalphalipoproteinemia is the most common lipoprotein abnormality in patients with coronary artery disease, yet its causes are unknown.
  
  
  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.
authors.affiliation: INSERM U141 and IFR "Circulation Lariboisière," Rhône-Poulenc Rorer, Gencell Division, Atherosclerosis Department, Centre de recherches de Vitry-Alfortville, France.
authors.forename: A
authors.initials: A
authors.lastname: Mamontova
authors.forename: S
authors.initials: S
authors.lastname: Séguret-Macé
authors.forename: B
authors.initials: B
authors.lastname: Esposito
authors.forename: C
authors.initials: C
authors.lastname: Chaniale
authors.forename: M
authors.initials: M
authors.lastname: Bouly
authors.forename: N
authors.initials: N
authors.lastname: Delhaye-Bouchaud
authors.forename: G
authors.initials: G
authors.lastname: Luc
authors.forename: B
authors.initials: B
authors.lastname: Staels
authors.forename: N
authors.initials: N
authors.lastname: Duverger
authors.forename: J
authors.initials: J
authors.lastname: Mariani
authors.forename: A
authors.initials: A
authors.lastname: Tedgui
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology; D016632:Apolipoprotein A-I / Q000097:blood / Q000235:genetics / Q000378:metabolism; D016633:Apolipoprotein A-II / Q000097:blood / Q000235:genetics; D001161:Arteriosclerosis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D001835:Body Weight; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D004036:Diet, Atherogenic; D005260:Female; D017353:Gene Deletion; D007413:Intestinal Mucosa / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000097:blood* / Q000172:deficiency*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D009419:Nerve Tissue Proteins / Q000235:genetics; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D012333:RNA, Messenger / Q000096:biosynthesis; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D008076:Cholesterol, HDL; D008075:Lipoproteins, HDL; D009419:Nerve Tissue Proteins; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D015534:Trans-Activators; D002784:Cholesterol