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Sickle Cell Disease Phenotypes in Townes & Berkeley Mouse Models

Stock Numbers 013071 & 003342

Townes model mice (B6;129-Hbbtm2(HBG1,HBB*)Tow/Hbbtm3(HBG1,HBB)TowHbatm1(HBA)Tow/J, 013071) develop sickle cell disease in the presence of human knock-in alleles that replace mouse α-globin and β-globin. The Berkeley model (STOCKHbatm1Paz Hbbtm1Tow Tg(HBA-HBBs)41Paz/J, 003342) also develops sickle cell disease due to a human hemoglobin transgene and deficiency in mouse α-globin and β-globin. Aspects of sickle cell disease include:

  • Elevated white blood cell & reticulocyte counts and increased mean red blood cell volume in females and males of both strains (Table 1, 2)
  • Reduced red blood cells, hemoglobin, and hematocrit in females and males of both strains (Table 1, 2)
  • Decreased mean corpuscular hemoglobin (females & males) and platelets (males) in the Berkeley model (Table 2)

Body weights and complete hematology data are available in the Mouse Phenome Database.

Table 1: Townes Model Hematology. Submental blood was collected into EDTA-coated microtainers and analyzed using a Siemens Advia 2120 hematology analyzer. Data represent mean and one standard deviation of 10 mice per sex and genotype, aged 8 weeks. Each parameter was analyzed separately by sex using a one-way ANOVA; an * indicates that the sickle genotype was significantly different (P < 0.0001) from both control genotypes. Each column header indicates the human beta-globin genotype and the JAX genotype ordering code.

 Townes Model FemalesTownes Model Males
 Sickle
(S/S; M21)		Control
(A/A; M22)		Corrected
(S/A; M23)		Sickle
(S/S; M21)		Control
(A/A; M22)		Corrected
(A/S; M23)

White blood cells (103/μL)

37.9 ± 9.1*13.1 ± 2.816.4 ± 3.529.7 ± 5.9*11.9 ± 3.012.9 ± 2.8

Red blood cells (106/μL)

8.2 ± 0.7*13.5 ± 0.513.5 ± 0.38.3 ± 1.0*13.8 ± 0.713.7 ± 0.5

Hemoglobin (g/dL)

7.8 ± 0.6*12.9 ± 0.512.6 ± 0.48.3 ± 1.0*13.2 ± 0.813.0 ± 0.6

Reticulocytes (%)

49.6 ± 4.3*6.2 ± 1.38.0 ± 1.948.7 ± 2.7*6.9 ± 3.46.7 ± 0.7

Reticulocytes (109/L)

4071 ± 444*827 ± 1701084 ± 2724026 ± 485*931 ± 411925 ± 113

Hematocrit (%)

36.9 ± 2.7*46.0 ± 1.444.6 ± 1.438.6 ± 4.5*47.9 ± 2.146.0 ± 1.9

Mean Cell Volume (fL)

45.0 ± 2.0*34.1 ± 0.532.9 ± 0.546.7 ± 0.7*34.8 ± 1.033.5 ± 0.6

Red Cell Distribution Width (%)

32.3 ± 3.831.7 ± 1.534.8 ± 2.430.3 ± 2.331.4 ± 3.332.0 ± 1.6

Mean Corpuscular Hemoglobin (pg)

9.5 ± 0.59.6 ± 0.29.3 ± 0.310.1 ± 0.39.6 ± 0.49.5 ± 0.2

Platelets (103/μL)

791 ± 191919 ± 1521068 ± 197614 ± 1691079 ± 1371194 ± 198

Table 2: Berkeley Model Hematology. Blood was collected as described in Table 1 from 8-12 mice per sex and genotype. Each parameter was analyzed separately by sex using an unpaired two-tailed t-test; an * indicates that the sickle genotype was significantly different (P < 0.0001) from the control genotype.

 Berkeley Model FemalesBerkeley Model Males
 Sickle
(Hom Hom Hemi)		Control
(Hom Het Hemi)		Sickle
(Hom Hom Hemi)		Control
(Hom Het Hemi)

White blood cells (103/μL)

20.0 ± 5.2*7.1 ± 2.525.1 ± 7.1*12.3 ± 1.5

Red blood cells (106/μL)

8.2 ± 0.5*12.1 ± 0.87.7 ± 0.5*12.8 ± 0.3

Hemoglobin (g/dL)

7.0 ± 0.5*12.1 ± 0.86.4 ± 0.5*12.3 ± 0.4

Reticulocytes (%)

36.0 ± 2.7*6.0 ± 2.240.7 ± 1.5*7.9 ± 0.8

Reticulocytes (109/L)

2946 ± 254*738 ± 2943124 ± 213*1010 ± 95

Hematocrit (%)

31.1 ± 2.0*39.0 ± 2.330.0 ± 2.0*40.2 ± 1.0

Mean Cell Volume (fL)

37.9 ± 1.0*32.4 ± 0.939.0 ± 1.1*31.4 ± 0.7

Red Cell Distribution Width (%)

33.2 ± 1.431.2 ± 2.033.6 ± 1.433.5 ± 1.1

Mean Corpuscular Hemoglobin (pg)

8.5 ± 0.2*10.1 ± 0.38.3 ± 0.2*9.6 ± 0.3

Platelets (103/μL)

695 ± 56576 ± 130598 ± 273*1162 ± 164
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