A targeted mutation in the murine gene encoding the high density lipoprotein (HDL) receptor scavenger receptor class B type I reveals its key role in HDL metabolism

• DOI: 10.1073/pnas.94.23.12610
• Publication Date: 2002-07-26T14:35:50Z
• Authors: Attilio Rigotti; Bernardo L. Trigatti; Marsha Penman; Helen Rayburn; Joachim Herz; Monty Krieger
• Keywords: Scavenger Receptor; Cholesteryl ester; Reverse cholesterol transport; High-density lipoprotein; Apolipoprotein E

Plasma high density lipoprotein (HDL), which protects against atherosclerosis, is thought to remove cholesterol from peripheral tissues and deliver cholesteryl esters via a selective uptake pathway the liver (reverse transport) steroidogenic (e.g., adrenal gland for storage hormone synthesis). Despite its physiologic pathophysiologic importance, cellular metabolism of HDL has not been well defined. The class B, type I scavenger receptor (SR-BI) proposed play an important role in because ( i ) it cell surface mediates cultured cells, ii physiologically regulated expression most abundant tissues, iii hepatic overexpression dramatically lowers plasma HDL. To test directly normal SR-BI metabolism, we generated mice with targeted null mutation gene. In heterozygous homozygous mutants relative wild-type controls, concentrations were increased by ≈31% 125%, respectively, formation large, apolipoprotein A-I (apoA-I)-containing particles, content decreased 42% 72%, respectively. concentration apoA-I, major protein HDL, was unchanged mutants. This, conjunction size, suggests that due uptake. These results provide strong support proposal gene encoding plays key determining levels (primarily HDL) accumulation stores gland. If similar controlling humans, may influence development progression atherosclerosis be attractive candidate therapeutic intervention this disease.