Mammalian Genome

, Volume 24, Issue 7–8, pp 257–265

A coding variant in SR-BI (I179N) significantly increases atherosclerosis in mice

  • Antonino Picataggi
  • Geoffrey F. Lim
  • Anthony P. Kent
  • John S. Millar
  • Daniel J. Rader
  • Ioannis M. Stylianou
Article

Abstract

Human coding variants in scavenger receptor class B member 1 (SR-BI; gene name SCARB1) have recently been identified as being associated with plasma levels of HDL cholesterol. However, a link between coding variants and atherosclerosis has not yet been established. In this study we set out to examine the impact of a SR-BI coding variant in vivo. A mouse model with a coding variant in SR-BI (I179N), identified through a mutagenesis screen, was crossed with Ldlr/ mice, and these mice were maintained on a Western-type diet to promote atherosclerosis. Mice showed 56 and 125 % increased atherosclerosis in female and male Ldlr/Scarb1I179N mice, respectively, when compared to gender-matched Ldlr/ control mice. As expected, HDL cholesteryl ester uptake was impaired in Ldlr/Scarb1I179N mice compared to Ldlr/ control mice, with a net effect of increased small and very small LDL cholesterol in Ldlr/Scarb1I179N mice being the most probable cause of the observed increased atherosclerosis. Our data show that non-null coding variants in SR-BI can have a large significant impact on atherosclerosis, even if plasma lipid levels are not dramatically affected, and that human mutations in other candidate lipid genes could significantly impact atherosclerosis.

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Antonino Picataggi
    • 1
  • Geoffrey F. Lim
    • 1
  • Anthony P. Kent
    • 1
  • John S. Millar
    • 1
  • Daniel J. Rader
    • 1
  • Ioannis M. Stylianou
    • 1
  1. 1.Institute for Translational Medicine and Therapeutics, School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA

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