Changes in alpha-globin gene expression in mice of two alpha-globin haplotypes during development

Abstract

Adult alpha-globin in mice is synthesized in large amounts during development, first in the primitive, nucleated erythrocytes of yolk sac origin and later in the definitive, nonnucleated erythrocytes that differentiate in the fetal liver, spleen, and bone marrow. Isoelectric focusing analysis of hemoglobins of mice with the Hbag2 and Hbac haplotypes shows that the ratios of alpha chain 1 to chain 5m and alpha chain 1 to chain 4 in adult hemoglobins from Hbag2 and Hbac mice, respectively, change between day 11.5 and day 16.5 of gestation in nucleated red cells, while no change occurs in nonnucleated red cells. The percentage ratios of the two different alpha-globin chains are different in Hbag2 and Hbac mice for EII, EIII, and adult hemoglobin. In nucleated red cells of yolk sac origin, differences and changes in alpha-globin ratios are a composite of changing globin gene transcription and posttranslational competitive affinities among globins to form embryonic and adult hemoglobin tetramers.

Endothelial cell α-globin and its molecular chaperone α-hemoglobin–stabilizing protein regulate arteriolar contractility

“…To investigate this possibility further, we evaluated baseline TDA diameters in Ahsp −/− and Hba1 −/− mice. Mouse α-globin is encoded by 2 tandem genes, Hba1 and Hba2, which are expressed at a 40:60 ratio in adult RBC (23). The TDAs of Ahsp −/− and Hba1 −/− mice appeared to be dilated compared with those of WT controls ( Figure 3, A and B).…”

Regulation of Iron Absorption in Hemoglobinopathies

“…Even with the addition of a human alpha-globin transgene, only a small fraction of the cells sickled in vivo because of the disruption of HbS by murine alpha-globin proteins [47]. In addition, under hypoxic conditions, there is more extensive deoxygenation of murine Hb than HbS, as mouse Hb has a lower O 2 affinity than HbS [48]. …”

Transgenic knockout mice exclusively expressing human hemoglobin S after transfer of a 240-kb β s -globin yeast artificial chromosome: A mouse model of sickle cell anemia

“…Heterotetramers of murine ␣-globin and human ␤ s -globin do not polymerize efficiently; even with the addition of human ␣-globin transgenes only a small fraction of the cells sickled in vivo because of the disruption of HbS by murine ␣-and ␤-globins (3)(4)(5)(6)(7)(8)(9)(10)(11). Under hypoxic conditions there is more extensive deoxygenation of murine hemoglobin than HbS, as mouse hemoglobin has a lower O 2 affinity than does HbS (12). To produce a hemoglobin that would polymerize more readily, two additional mutations were introduced into ␤ s transgenes; a second mutation in codon 23 to reproduce the ␤ s Antilles allele, and a third mutation to yield ␤ s AntillesD Punjab or HbSAD (6,7,13).…”