{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T07:50:53Z","timestamp":1778658653154,"version":"3.51.4"},"reference-count":86,"publisher":"American Physiological Society","issue":"6","funder":[{"name":"HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI)","award":["HL077780"],"award-info":[{"award-number":["HL077780"]}]},{"name":"HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI)","award":["HL127174"],"award-info":[{"award-number":["HL127174"]}]},{"name":"HHS | National Institutes of Health (NIH)","award":["T32GM007287"],"award-info":[{"award-number":["T32GM007287"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2016,12,1]]},"abstract":"<jats:p>The HDL receptor SR-BI mediates the transfer of cholesteryl esters from HDL to cells and controls HDL abundance and structure. Depending on the genetic background, loss of SR-BI causes hypercholesterolemia, anemia, reticulocytosis, splenomegaly, thrombocytopenia, female infertility, and fatal coronary heart disease (CHD). The carboxy terminus of SR-BI (<jats:sup>505<\/jats:sup>QEAKL<jats:sup>509<\/jats:sup>) must bind to the cytoplasmic adaptor PDZK1 for normal hepatic\u2014but not steroidogenic cell\u2014expression of SR-BI protein. To determine whether SR-BI's carboxy terminus is also required for normal protein levels in steroidogenic cells, we introduced into SR-BI's gene a<jats:sup>507<\/jats:sup>Ala\/STOP mutation that produces a truncated receptor (SR-BI\u0394CT). As expected, the dramatic reduction of hepatic receptor protein in SR-BI\u0394CT mice was similar to that in PDZK1 knockout (KO) mice. Unlike SR-BI KO females, SR-BI\u0394CT females were fertile. The severity of SR-BI\u0394CT mice's hypercholesterolemia was intermediate between those of SR-BI KO and PDZK1 KO mice. Substantially reduced levels of the receptor in adrenal cortical cells, ovarian cells, and testicular Leydig cells in SR-BI\u0394CT mice suggested that steroidogenic cells have an adaptor(s) functionally analogous to hepatic PDZK1. When SR-BI\u0394CT mice were crossed with apolipoprotein E KO mice (SR-BI\u0394CT\/apoE KO), pathologies including hypercholesterolemia, macrocytic anemia, hepatic and splenic extramedullary hematopoiesis, massive splenomegaly, reticulocytosis, thrombocytopenia, and rapid-onset and fatal occlusive coronary arterial atherosclerosis and CHD (median age of death: 9 wk) were observed. These results provide new insights into the control of SR-BI in steroidogenic cells and establish SR-BI\u0394CT\/apoE KO mice as a new animal model for the study of CHD.<\/jats:p>","DOI":"10.1152\/ajpheart.00463.2016","type":"journal-article","created":{"date-parts":[[2016,10,1]],"date-time":"2016-10-01T02:39:48Z","timestamp":1475289588000},"page":"H1392-H1408","source":"Crossref","is-referenced-by-count":22,"title":["Carboxy-terminal deletion of the HDL receptor reduces receptor levels in liver and steroidogenic tissues, induces hypercholesterolemia, and causes fatal heart disease"],"prefix":"10.1152","volume":"311","author":[{"given":"Rinku","family":"Pal","sequence":"first","affiliation":[{"name":"Department of Pathology and Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, 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