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Blood, 15 February 2006, Vol. 107, No. 4, pp. 1651-1658. Prepublished online as a Blood First Edition Paper on September 15, 2005; DOI 10.1182/blood-2005-07-2839.
RED CELLS Pathology of Berkeley sickle cell mice: similarities and differences with human sickle cell diseaseFrom The Department of Pathology, Centralized Pathology Unit for Sickle Cell Disease, University of South Alabama, Mobile; the Medical College of Wisconsin and The Blood Center of Southeastern Wisconsin, Milwaukee; the Department of Anesthesiology, Mount Sinai School of Medicine, New York, NY; the Department of Neurology, Henry Ford Hospital, Detroit, MI; the Wilmer Ophthalmological Institute, Johns Hopkins Hospital, Baltimore, MD; and the Laboratory of Blood and Vascular Biology, The Rockefeller University, New York, NY.
Because Berkeley sickle cell mice are used as an animal model for human sickle cell disease, we investigated the progression of the histopathology in these animals over 6 months and compared these findings to those published in humans with sickle cell disease. The murine study groups were composed of wild-type mixed C57Bl/6-SV129 (control) mice and sickle cell (SS) mice (
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| Copyright © 2006 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||||
-/-, 
-/-, transgene +) of both sexes and between 1 and 6 months of age. SS mice were similar to humans with sickle cell disease in having erythrocytic sickling, vascular ectasia, intravascular hemolysis, exuberant hematopoiesis, cardiomegaly, glomerulosclerosis, visceral congestion, hemorrhages, multiorgan infarcts, pyknotic neurons, and progressive siderosis. Cerebral perfusion studies demonstrated increased blood-brain barrier permeability in SS mice. SS mice differed from humans with sickle cell disease in having splenomegaly, splenic hematopoiesis, more severe hepatic infarcts, less severe pulmonary manifestations, no significant vascular intimal hyperplasia, and only a trend toward vascular medial hypertrophy. Early retinal degeneration caused by a homozygous mutation (rd1) independent from that causing sickle hemoglobin was an incidental finding in some Berkeley mice. While our study reinforces the fundamental strength of this model, the notable differences warrant careful consideration when drawing parallels to human sickle cell disease. 
