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Updated: May 11, 2026
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Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
A coding variant in SR-BI (I179N) significantly increases atherosclerosis in mice
Antonino Picataggi1, Geoffrey F Lim, Anthony P Kent
1Institute for Translational Medicine and Therapeutics, School of Medicine, University of Pennsylvania, 654 BRBII/III Labs, 421 Curie Boulevard, Philadelphia, PA 19104-6160, USA.
Summary
Human scavenger receptor class B member 1 (SR-BI) coding variants increase atherosclerosis risk. This study shows SR-BI variants significantly promote atherosclerosis in mice, even without major plasma lipid changes, highlighting potential risks from other lipid gene mutations.
Area of Science:
- Cardiovascular Biology
- Genetics
- Metabolic Diseases
Background:
- Human coding variants in scavenger receptor class B member 1 (SR-BI) are linked to HDL cholesterol levels.
- A direct association between SR-BI coding variants and atherosclerosis has not been established.
Purpose of the Study:
- To investigate the in vivo impact of a specific SR-BI coding variant on atherosclerosis development.
- To determine if SR-BI coding variants contribute to atherosclerosis independently of significant plasma lipid alterations.
Main Methods:
- A mouse model with an SR-BI coding variant (I179N) was generated.
- This model was crossed with Ldlr (-/-) mice and fed a Western-type diet to induce atherosclerosis.
- Atherosclerosis progression and HDL cholesteryl ester uptake were analyzed.
Main Results:
- SR-BI variant mice exhibited significantly increased atherosclerosis: 56% in females and 125% in males compared to controls.
- HDL cholesteryl ester uptake was impaired in SR-BI variant mice.
- Increased small and very small LDL cholesterol levels were identified as a likely cause of heightened atherosclerosis.
Conclusions:
- Non-null coding variants in SR-BI can substantially increase atherosclerosis risk.
- The impact on atherosclerosis can occur even when plasma lipid levels are not dramatically altered.
- Human mutations in other lipid-related genes may also significantly influence atherosclerosis development.
