Hemoglobin variants in Koreans: hemoglobin G Taegu

Hemoglobin G Taegu, an electrophoretically slow hemoglobin with a structural anomaly believed to be in the beta-T-3 section of the beta chain, was the only variant found among 6700 normal Koreans. Four subjects, 0.06 percent, had the G-hemoglobin variant in addition to normal hemoglobin A. Hemoglobin E, known in numerous groups from Southeast Asia and the variant most frequently seen in Chinese subjects, was not found among the Koreans we tested.     

Human sickle hemoglobin in transgenic mice

DNA molecules that contain the human alpha- and beta s-globin genes inserted downstream of erythroid-specific, deoxyribonuclease I super-hypersensitive sites were coinjected into fertilized mouse eggs and a transgenic mouse line was established that synthesizes human sickle hemoglobin (Hb S). These animals were bred to beta-thalassemic mice to reduce endogenous mouse globin levels. When erythrocytes from these mice were deoxygenated, greater than 90 percent of the cells displayed the same characteristic sickled shapes as erythrocytes from humans with sickle cell disease. Compared to controls the mice have decreased hematocrits, elevated reticulocyte counts, lower hemoglobin concentrations, and splenomegaly, which are all indications of the anemia associated with human sickle cell disease.     

Synthesis of functional human hemoglobin in transgenic mice

Human alpha- and beta-globin genes were separately fused downstream of two erythroid-specific deoxyribonuclease (DNase) I super-hypersensitive sites that are normally located 50 kilobases upstream of the human beta-globin gene. These two constructs were coinjected into fertilized mouse eggs, and expression was analyzed in transgenic animals that developed. Mice that had intact copies of the transgenes expressed high levels of correctly initiated human alpha- and beta-globin messenger RNA specifically in erythroid tissue. An authentic human hemoglobin was formed in adult erythrocytes that when purified had an oxygen equilibrium curve identical to the curve of native human hemoglobin A (Hb A). Thus, functional human hemoglobin can be synthesized in transgenic mice. This provides a foundation for production of mouse models of human hemoglobinopathies such as sickle cell disease.     

Inherited electrophoretic hemoglobin patterns among 20 inbred strains of mice

The hemoglobin from mice of six inbred strains is of the single-spot electrophoretic type, and that from 14 inbred strains is of the diffuse type. No selective advantage is apparent for either type. The distribution among strains shows some relation to the history of the development of the strains.     

Correction of sickle cell disease in adult mice by interference with fetal hemoglobin silencing

Persistence of human fetal hemoglobin (HbF, α(2)γ(2)) in adults lessens the severity of sickle cell disease (SCD) and the β-thalassemias. Here, we show that the repressor BCL11A is required in vivo for silencing of γ-globin expression in adult animals, yet dispensable for red cell production. BCL11A serves as a barrier to HbF reactivation by known HbF inducing agents. In a proof-of-principle test of BCL11A as a potential therapeutic target, we demonstrate that inactivation of BCL11A in SCD transgenic mice corrects the hematologic and pathologic defects associated with SCD through high-level pancellular HbF induction. Thus, interference with HbF silencing by manipulation of a single target protein is sufficient to reverse SCD.     

Fetal research

This article reviews some of the significant contributions of fetal research and fetal tissue research over the past 20 years. The benefits of fetal research include the development of vaccines, advances in prenatal diagnosis, detection of malformations, assessment of safe and effective medications, and the development of in utero surgical therapies. Fetal tissue research benefits vaccine development, assessment of risk factors and toxicity levels in drug production, development of cell lines, and provides a source of fetal cells for ongoing transplantation trials. Together, fetal research and fetal tissue research offer tremendous potential for the treatment of the fetus, neonate, and adult.     

Conformational equilibria in spin-labeled hemoglobin

A component characteristic of deoxyhemoglobin appears in the paramagnetic resonance spectrum of spin-labeled oxyhemoglobin, and vice versa, under conditions of pH and ionic strength consistent with the interpretation that the spectrum is sensitive to the conformational equilibrium of the carboxy-terminal histidines. The oxygenation-induced change in the resonance spectrum is discussed in terms of shifts in this equilibrium.     

Gelation of sickle cell hemoglobin: effects of hybrid tetramer formation in hemoglobin mixtures

The altered gelation behavior found in mixtures of sickle cell hemoglobin with other hemoglobins is due to the formation of hybrid hemoglobin tetramers from unlike dimers. The hemoglobins need not possess the deoxy quaternary structure for gelation to occur; liganded forms are also capable of participation in gelation.     

Electrophoresis of hemoglobin in single erythrocytes

A technique for electrophoretic analysis of the hemoglobin mixtures from single erythrocytes has been developed. Hemoglobin mixtures were separated into their constituents, A(2), A, C, S, and J, at least qualitatively.