Summary of similarities and differences or limitations of using humanized HbSS mouse model
| PROS . | CONS . |
|---|---|
| HbSS mice exclusively express human sickle hemoglobin: mouse α-globin genes are replaced with human α-globin HBA1 gene, mouse β-like globin genes replaced with tandemly linked genomic segments of human γ-globin HGB1 and sickle β-globin HBBSgenes. | HbSS mice almost immediately after birth switch HbF to HbS. |
| HbSS mice present hematological similarities with human SCA: erythrocytic sickling, intravascular hemolysis, reticulocytosis, anemia, leukocytosis. | HbSS mice have heterogenic genetic background, which may result in genetic drift. |
| HbSS mice present histopathological similarities with human SCA: multiorgan infarcts, endothelial dysfunction, inflammation, vasculopathy, heart hypertrophy, pulmonary hypertension, hepatic iron overload and fibrosis, nociception. | Owing to species specific characteristics HbSS mice may present with different pharmacokinetics and/or drug metabolism. |
| HbSS mice recapitulates human renal phenotype: early hyperfiltration, progressive albuminuria/proteinuria, progressive GFR decline, glomerulopathy, tubulopathy, hypostenuria, and papillary congestion/necrosis. | |
| HbSS mice are widely available, easy to maintain, cost-effective, suitable for longitudinal studies, provide ability to model disease through pharmacological, genetic, cellular, surgical manipulations, valuable for preclinical studies. | |
| Advantages of using HbSS over other animal SCA models: Humanized porcine SCA animal model represents prolonged HbF to HbS switch (∼12 months); it is unknown if this model recapitulate human disease; limited availability and high cost of maintenance of the model. Baboon model presents a great model to study HbF-inducing treatments (β-like globin gene locus is highly conserved between baboon and man) but does not exhibit SCA pathology (owing to the lack of HbS). Berkeley sickle cell mouse model lacks proper genetic (littermate) controls; has reduced mean corpuscular Hb concentration (mild α-thalassemia phenotype); has exuberant splenic hematopoiesis. SAD mouse express mouse α- and βminor and human SAD hemoglobin transgene (low proportion of human SAD Hb); is not anemic, recapitulates only some SCA-associated kidney defects. |
| PROS . | CONS . |
|---|---|
| HbSS mice exclusively express human sickle hemoglobin: mouse α-globin genes are replaced with human α-globin HBA1 gene, mouse β-like globin genes replaced with tandemly linked genomic segments of human γ-globin HGB1 and sickle β-globin HBBSgenes. | HbSS mice almost immediately after birth switch HbF to HbS. |
| HbSS mice present hematological similarities with human SCA: erythrocytic sickling, intravascular hemolysis, reticulocytosis, anemia, leukocytosis. | HbSS mice have heterogenic genetic background, which may result in genetic drift. |
| HbSS mice present histopathological similarities with human SCA: multiorgan infarcts, endothelial dysfunction, inflammation, vasculopathy, heart hypertrophy, pulmonary hypertension, hepatic iron overload and fibrosis, nociception. | Owing to species specific characteristics HbSS mice may present with different pharmacokinetics and/or drug metabolism. |
| HbSS mice recapitulates human renal phenotype: early hyperfiltration, progressive albuminuria/proteinuria, progressive GFR decline, glomerulopathy, tubulopathy, hypostenuria, and papillary congestion/necrosis. | |
| HbSS mice are widely available, easy to maintain, cost-effective, suitable for longitudinal studies, provide ability to model disease through pharmacological, genetic, cellular, surgical manipulations, valuable for preclinical studies. | |
| Advantages of using HbSS over other animal SCA models: Humanized porcine SCA animal model represents prolonged HbF to HbS switch (∼12 months); it is unknown if this model recapitulate human disease; limited availability and high cost of maintenance of the model. Baboon model presents a great model to study HbF-inducing treatments (β-like globin gene locus is highly conserved between baboon and man) but does not exhibit SCA pathology (owing to the lack of HbS). Berkeley sickle cell mouse model lacks proper genetic (littermate) controls; has reduced mean corpuscular Hb concentration (mild α-thalassemia phenotype); has exuberant splenic hematopoiesis. SAD mouse express mouse α- and βminor and human SAD hemoglobin transgene (low proportion of human SAD Hb); is not anemic, recapitulates only some SCA-associated kidney defects. |
GFR, glomerular filtration rate; HbF, fetal hemoglobin; HbS, sickle hemoglobin; SAD, Hemoglobin beta S-Antilles-D Punjab.