Table 1.

Murine models of sickle cell disease, thalassemias and Cooley’s anemia

	Genotype	Phenotype	Severity of disease
SCD mouse model
S Antilles	α^H β^{S Antilles}	Mild adult anemia Low irreversible sickling	Mild
S+S Antilles	α^H β^S β^{S Antilles}	Neonatal anemia Significant sickling	Mild—moderate
SAD	α^H β^SAD	Neonatal anemia Low irreversible sickling Multi-organ pathology	Moderate
Berkeley model (murine knockout)	α^H β^S γ^H δ^H	Significant adult anemia High irreversible sickling Chronic multi-organ damage	Moderate—severe
Birmingham model (murine knockout)	α^H β^S γ^H	Severe anemia High irreversible sickling Multi-organ pathology	Moderate—severe
San Francisco model (murine knockout)	α^H β^S γ^H δ^H (YAC)	Anemia Irreversible sickling	Moderate—severe
Enhanced γ-globin expression models	α^H β^S (γ^Ha/γ^Hb/γ^Hc) and α^H β^SAD γ^H	Decreased severity of disease with increasing HbF levels	Moderate—severe
Thalassemia mouse model
Carolina β⁰ (murine knockout)	Δb1/b2	Heterozygous mice dramatically decreased hematocrit, hemoglobin, red blood cell counts, MCV, MCH, and MCHC, dramatically increased reticulocyte counts, serum bilirubin concentrations, and red cell distribution widths, display tissue and organ damage, spontaneous iron overload in spleen, liver, kidneys Homozygous mice: die in utero	Severe
Birmingham β⁰ (murine knockout)	Δβ^maj/β^min	Heterozygous mice: severely anemic, dramatically reduced hemoglobin levels, abnormal red cell morphology, splenomegaly, markedly increased reticulocyte counts Homozygous mice: die in utero	Severe
βIVS-2-654 (murine knockout/human knock-in)	Δβ^maj/β^min/HuβIVS-2–654	Heterozygous mice: reduced mouse β globin chains and no human β globin Homozygous mice: do not survive postnatally	Moderate
Cooley’s anemia (β thalassemia major) (murine knockout/human knock-in)	Δβ^maj/β^min/Hu γβ⁰ Δα1/α2/Hu Δα2/α1	Heterozygous γβ⁰ knock-in mice: β thalassemia intermedia Homozygous mice: expire due to severe anemia upon completion of the HbF to adult switch after birth	Severe
Cooley’s anemia (β thalassemia major) Preclinical model (murine knockout/human knock-in)	Δβ^maj/β^min/Hu γ^HPFHδβ⁰ Δα1/α2/Hu Δα2/α1	Fully humanized mice survive postnatally by synthesizing predominantly HbF, some HbA2, completion of fetal to adult Hb switch after birth results in severe anemia marked by erythroid hyperplasia, ineffective erythropoiesis, hemolysis, and death	Severe
Berkeley α (murine knockout)	Δα1/α2	Homozygous mice: become hydropic, die late in gestation, model for human hydrops fetalis	Severe

α^H, γ^H, δ^H, human α-, γ- and δ-globin genes; β^S, human β-globin gene with HbS mutation; β^{S Antilles}, human β-globin gene with HbS Antilles mutation; β^SAD, human β-globin gene with HbS, HbS Antilles and HbD Punjab mutations; γ^Ha/γ^Hb/γ^Hc: human γ-globin genes expressing three different levels of HbF. See text for references