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MGI Accession ID: MGI:2175936
J Number: J:75090
Other Accession IDs: Title: Failure of red blood cell maturation in mice with defects in the high-density lipoprotein receptor SR-BI.
Authors: Holm TM; Braun A; Trigatti BL; Brugnara C; Sakamoto M; Krieger M; Andrews NC
Journal: Blood
Volume: 99
Issue: 5
Date: 2002 Mar 1
Year: 2002
Pages: 1817-24
Review Status: Peer Reviewed

Abstract:

Mammalian erythrocytes undergo a unique maturation process in which they discard their nuclei and organelles and assume a flexible biconcave shape. We found that altered plasma lipoprotein metabolism can profoundly influence these events. Abnormal erythrocyte morphology was observed in hypercholesterolemic mice lacking the high-density lipoprotein receptor SR-BI. This was exacerbated by feeding mice a high-cholesterol diet or, more dramatically, by inactivating the apolipoprotein E gene. Erythrocytes from SR-BI(-/-)/apolipoprotein E(-/-) mice and SR-BI(-/-) mice that were fed cholesterol had markedly increased membrane cholesterol. Their morphology appeared immature, with macrocytosis, irregular shape, and large autophagolysosomes. Autophagolysosomes from SR-BI(-/-)/apolipoprotein E(-/-) erythrocytes were expelled when the erythrocytes were transfused into wild-type animals or incubated in vitro with normolipidemic serum or the cholesterol-sequestering agent methyl cyclodextrin. We propose that autophagocytosis and phagolysosome expulsion are essential steps in erythroid maturation and that expulsion is inhibited in the presence of markedly increased cellular cholesterol.

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