Related Experiment Video
Updated: Aug 15, 2026
A Mouse Model of Vascularized Heterotopic Spleen Transplantation for Studying Spleen Cell Biology and Transplant Immunity
Published on: June 11, 2019
Pathology of Berkeley sickle cell mice: similarities and differences with human sickle cell disease
Elizabeth A Manci1, Cheryl A Hillery, Carol A Bodian
1Department of Pathology, Centralized Pathology Unit for Sickle Cell Disease, University of South Alabama, Mobile, AL 36604, USA. emanci@usouthal.edu
Abstract:
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.
Insights
The Berkeley sickle cell mouse model shows similarities and differences to human sickle cell disease progression over six months. Careful consideration of these variations is crucial when comparing animal study results to human patients.
Area of Science:
- Hematology
- Pathology
- Animal Models
Background:
- Sickle cell disease (SCD) is a genetic blood disorder with significant morbidity and mortality.
- Animal models are essential for understanding SCD pathogenesis and testing therapies.
- The Berkeley sickle cell mouse model is frequently used, necessitating a thorough evaluation of its fidelity to human SCD.
Purpose of the Study:
- To investigate the histopathological progression of the Berkeley sickle cell mouse model over six months.
- To compare the observed histopathology in mice with established findings in human SCD.
- To identify similarities and differences that may impact the translational relevance of this model.
Main Methods:
- Longitudinal study of wild-type and sickle cell (SS) mice from 1 to 6 months of age.
- Histopathological analysis of multiple organs.
- Cerebral perfusion studies to assess blood-brain barrier permeability.
- Comparison of murine findings with published human SCD data.
Main Results:
- SS mice exhibited key SCD features: sickling, hemolysis, vascular changes, organ damage (heart, kidneys, brain), and hematopoiesis.
- Increased blood-brain barrier permeability was observed in SS mice.
- Differences included splenomegaly, splenic hematopoiesis, more severe liver infarcts, and less severe pulmonary issues in mice.
- Absence of significant intimal hyperplasia and only a trend toward medial hypertrophy were noted in mice.
Conclusions:
- The Berkeley sickle cell mouse model largely recapitulates human SCD histopathology, validating its utility.
- Specific differences, such as splenic involvement and vascular remodeling, require careful consideration for translational research.
- Incidental findings, like retinal degeneration, highlight the importance of genetic background in model interpretation.
