In complete α-globin deficiency, erythrocytes carry hemoglobin Bart’s (γ4 tetramer), which does not effectively deliver oxygen, leading to the BHFS and resulting in fetal demise. Here Chappell et al report a novel conditional mouse model of severe α-thalassemia based on a floxed α-globin allele, ex vivo Cre delivery to HSCs by LNPs, and hematopoietic transplant. In these animals with complete α-globin deficiency in the adult stage where erythrocytes carry nonfunctional Hb H (β4 tetramer), erythrocytosis and tissue hypoxia preceded lethality, which could be rescued by a novel α-globin lentiviral vector. Professional illustration by Somersault18:24.
