The b-thalassemias are caused by more than 200 mutations that reduce or abolish b-globin production. The severity of the resulting anemia can lead to lifelong transfusion dependency.Agenetic treatment based on globin gene transfer would require that transgene expression be erythroid specific, elevated, and sustained over time. We report here that long-term synthesis of chimeric hemoglobin (mua2...

Hemoglobin of Gastrophilus intestinalis (Insecta, Diptera), was purified and characterized. At least two isoforms have been identified by isoelectrofocusing, mass spectrometry, and genomic Southern blotting. Functional studies show a high oxygen affinity due to a low ligand dissociation rate (koff = 2.4 s-1) and a relatively high autoxidation rate (t1/2 = 1.6/h). The globins were separated unde...

Unexpected clonal variability was observed in the content of beta-globin mRNA in erythropoietin receptor (EpoR)-transfected Ba/F3 cells before and after exposure to erythropoietin (Epo). Of 11 clones selected by virtue of G418 resistance and positive EpoR expression, 5 clones showed high levels of beta(major)-globin mRNA before Epo exposure, with subsequent Epo treatment causing little or no in...

1. The globin prepared from hemoglobin by the acid acetone method is denatured globin. 2. The denaturation and coagulation of globin by acid acetone are reversible. 3. Soluble globin can be obtained from the acid acetone globin even if the globin is first precipitated by trichloracetic acid or heated to 100 degrees C. 4. Hill and Holden's theory that they separated native globin from hemoglobin...

We have previously described the development of oncoretrovirus vectors for human -globin using a truncated -globin promoter, modified -globin cassette, and -globin enhancer. However, one of these vectors is genetically unstable, and both vectors exhibit variable expression patterns in cultured cells, common characteristics of oncoretrovirus vectors for globin genes. To address these problems, w...

We introduced a normal chromosome 11 into GM979 murine erythroleukemia cells by fusing them with Epstein-Barr virus-transformed lymphocytes from a normal individual. In contrast to previous data obtained with other murine erythroleukemia cells, we detected activation of human chromosomal gamma-globin genes in GM979 cells. GM979, unlike previously used murine erythroleukemia cell lines, expresse...

The DNaseI hypersensitive sites (HSs) of the human β-globin locus control region (LCR) may function as part of an LCR holocomplex within a larger active chromatin hub (ACH). Differential activation of the globin genes during development may be controlled in part by preferential interaction of each gene with specific individual HSs during globin gene switching, a change in conformation of the LC...

{-Globin is the embryonic form of the O( chain of hemoglobin. Transgenic mice generated with {-globin constructs containing the {-globin gene, 557 bp of 5 flanking sequence, and 2-kb of 3 flanking sequence linked to the @globin locus control region hypersensitive site 2 (HS2) expressed human {-globin only in embryonic yolk sac erythroid tissue, and not in definitive erythroid tissue in the feta...

Synthesis of alpha-globin and alpha-globin subunits of hemoglobin occurs at high levels during erythrocyte differentiation in a tightly controlled and coordinated fashion. Expression of alpha-globin is a fascinatingly complex process which has been meticulously defined in several recent studies, from chromatin modifications to Pol II recruitment. Following this, alpha-globin transcripts are pro...