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Related Experiment Videos

The "CholesteROR" protective pathway in the vascular system.

Fatiha Boukhtouche1, Jean Mariani, Alain Tedgui

  • 1Laboratoire Développement et Vieillissement du Système Nerveux, Université P. & M. Curie-CNRS, UMR NPA 7102, case 14, 9 quai Saint Bernard, 75005 Paris, France.

Arteriosclerosis, Thrombosis, and Vascular Biology
|January 31, 2004
PubMed
Summary

Retinoic acid receptor-related Orphan Receptor alpha (RORalpha), a nuclear receptor, is regulated by cholesterol. Loss of RORalpha function in mice leads to cerebellar degeneration and vascular issues, including atherosclerosis.

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Area of Science:

  • Molecular biology
  • Genetics
  • Neurobiology

Background:

  • Retinoic acid receptor-related Orphan Receptor alpha (RORalpha) is a nuclear hormone receptor.
  • Previously considered a constitutive transcriptional activator, RORalpha's natural ligand is now known to be cholesterol.
  • The staggerer (sg/sg) mutation in the Rora gene results in a non-functional ligand-binding domain (LBD).

Purpose of the Study:

  • To investigate the physiological roles of RORalpha, particularly its involvement in cholesterol regulation and vascular function.
  • To characterize the phenotypes associated with the loss of RORalpha activity due to the sg/sg mutation.

Main Methods:

  • Utilized the homozygous Rora(sg/sg) mutant mouse model.
  • Observed and analyzed phenotypes, focusing on cerebellar degeneration and vascular abnormalities.

Related Experiment Videos

  • Investigated RORalpha's role in regulating gene expression, including apolipoprotein (apo)A-I and apoC-III.

    • Main Results:

    • Homozygous Rora(sg/sg) mice exhibit ataxia and cerebellar degeneration.
    • These mice display vascular phenotypes, including smooth muscle cell dysfunction and increased susceptibility to atherosclerosis.
    • RORalpha plays a role in regulating plasma cholesterol levels and positively influences apoA-I and apoC-III gene expression.

    Conclusions:

    • RORalpha is an intracellular cholesterol target, with its activity modulated by cholesterol levels.
    • Loss of RORalpha function has significant implications for both neurological and vascular health.
    • RORalpha is a key regulator of cholesterol homeostasis and vascular integrity.