Pathology of Berkeley sickle cell mice: similarities and differences with human sickle cell disease. Blood 2006 Feb 15;107(4):1651-8
Date
09/17/2005Pubmed ID
16166585Pubmed Central ID
PMC1895417DOI
10.1182/blood-2005-07-2839Scopus ID
2-s2.0-32644437616 (requires institutional sign-in at Scopus site) 118 CitationsAbstract
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 (alpha-/-, beta-/-, 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.
Author List
Manci EA, Hillery CA, Bodian CA, Zhang ZG, Lutty GA, Coller BSMESH terms used to index this publication - Major topics in bold
Anemia, Sickle CellAnimals
Body Weight
Humans
Mice
Mutation
Organ Size
Reference Values
Species Specificity
