Mean values are listed with the standard error of the mean. Symbols by values indicate significance (P ≤ .5) between 2 cohorts for that parameter, with comparisons made as indicated in the table legend. Significant differences were determined using a Brown-Forsythe and Welch analysis of variance with Dunnett T3 multiple comparisons test. Male and female AG-KO^ALS20αI mice were compared for each parameter, and no significant differences were found. Statistical analyses were then performed on samples pooled from male and female animals. “→” indicates HSC transplants using cells from the donor mice into recipient mice. Differences between the heterozygous Hba-a1^KO/+/Hba-a2^KO/+ constitutive KO animals and homozygous Hba-a1^cKO/cKO/Hba-a2^KO/KO are likely due to differential levels of α-globin expression from different α-globin genes, a known effect in humans. HBA2 and its ortholog Hba-a1 are expressed at higher levels than HBA1 and Hba-a2.^39-41Hba-a1 is analogous to HBA2 in humans, which is 5′ of HBA1, and appears to be dominantly expressed. Therefore, because Hba-a1^KO/+/Hba-a2^KO/+ mice are missing 1 Hba-a1 and 1 Hba-a2, it is reasonable to predict that they would have a more severe phenotype than Hba-a1^cKO/cKO/Hba-a2^KO/KO mice that are missing 2 Hba-a2 genes.

Hb, hemoglobin; HCT, hematocrit; MCH, mean corpuscular Hb; MCHC, mean corpuscular Hb concentration; MCV, mean corpuscular volume; RBC, red blood cells; RDW-CV, coefficient of variation in red cell distribution width; RET, reticulocyte; RET%, percentage of reticulocytes.

Comparison between groups 1 and 4 (WT and AG-KO)

Comparison between groups 1 and 3 (WT and Hba-a1^ko/+/Hba-a2^ko/+)

Comparison between groups 6 and 1 (AG-KO^ALS20αI and WT)

Comparison between groups 2 and 3 (Hba-a1^Fl/Fl/Hba-a2^ko/KO and Hba-a1^ko/+/Hba-a2^ko/+)

Comparison between groups 6 and 3 (AG-KO^ALS20αI and Hba-a1^ko/+/Hba-a2^ko/+)

Comparison between groups 6 and 4 (AG-KO^ALS20αI and AG-KO)

Comparison between groups 4 and 5 (AG-KO and AG-FKO), no differences were observed.