Disease relevance of Hbb-b2

• Compensatory increase in levels of beta minor globin in murine beta-thalassemia is under translational control [1].
• Under these conditions the ratio of accumulated beta maj and beta min mRNA sequences approximates the 4:1 ratio observed in reticulocytes and murine erythroleukemia cells (MELC) induced to differentiate by hexamethylene bisacetamide (HMBA) [2].

High impact information on Hbb-b2

• Here we report a 16-kb deletion that includes both adult beta-like globin genes, beta maj and beta min, in mouse embryonic stem cells [3].
• The marked beta-major gene can be tracked at the level of DNA, RNA, and protein, allowing investigation of the impact of a retained phosphoglycerate kinase (PGK)-neo cassette located between the mutant beta-major and beta-minor globin genes on expression of these 2 neighboring genes [4].
• Lack of neighborhood effects from a transcriptionally active phosphoglycerate kinase-neo cassette located between the murine beta-major and beta-minor globin genes [4].
• A 1-year follow-up of 12 treated animals showed a stable correction of anemia associated with improved RBC morphology, increased beta-minor globin synthesis, and decreased amounts of alpha-globin chains bound to erythrocyte membranes [5].
• This study indicates that the continuous delivery of high amounts of autologous erythropoietin induced a sustained stimulation of beta-minor globin synthesis and a stable improvement of erythropoiesis in the beta-thalassemic mouse model [5].

Chemical compound and disease context of Hbb-b2

• Friend erythroleukemia clone 745 cells were induced to differentiate by dimethyl sulfoxide (Me2SO) or by hemin treatment, and nuclear transcripts of the beta major and beta minor globin genes examined [6].
• Processing of the beta major and beta minor globin pre-mRNAs has been compared in murine erythroleukemia cells induced to synthesize hemoglobin by dimethyl sulfoxide or hemin treatment, using both the Northern blot technique and S1 nuclease mapping with 3' and 5' end-labeled probes [7].

Biological context of Hbb-b2

• In Hbb-b1 cDNA, six base substitutions were found between the d and w1 haplotypes and also between p and w1, but none existed between d and p. In Hbb-b2 cDNA, three base substitutions were found between the d and w1 haplotypes and also between d and p, but none between p and w1 [8].
• beta-Minor globin gene expression is preferentially reduced in EKLF Knock-Out mice [9].
• Transfected intact mouse alpha 1-globin genes generate transcripts, whereas beta maj and beta min globin transcripts are detected only if the genes are associated with a strong exogenous (SV40) enhancer sequence [2].
• In normal mice, dysregulated Epo production induced elevated serum Epo levels (176 +/- 68 mU/mL), high hematocrit levels (73% +/- 8%), and elevated beta-minor globin chain synthesis [10].
• Transcription from the beta major and beta minor globin genes was measured separately by hybridization to cloned DNA sequences from a region of the second intron which is highly divergent in the two genes [11].

Anatomical context of Hbb-b2

• Elevated synthesis of beta minor globin is maintained during in vitro translation in thalassemic reticulocyte lysate [1].
• The time of replication in S phase was determined for the 7.3 kb EcoRI segment containing the beta-major globin gene and the 14 kb EcoRI segment containing the beta-minor globin gene in a murine Friend erythroleukemia virus transformed (MEL) cell line [12].
• Circulating red blood cells essentially synthesized beta-minor globin, the mouse equivalent to human gamma-globin [13].

Associations of Hbb-b2 with chemical compounds

• Butyric acid treatment led to approximately 40% beta-minor globin, while induction with hemin resulted in over 80% beta-minor synthesis [14].
• DMSO induction led to less than 10% beta-minor globin, while hemin and butyric acid both resulted in approximately 40% beta-minor synthesis [14].
• The results show that, during dimethyl sulfoxide-stimulated differentiation, transcription of alpha and beta major globin increases 15-25-fold, whereas beta minor globin transcription is not increased [11].

Other interactions of Hbb-b2

• Comparisons of this complex with that from the laboratory mouse, Mus domesticus (with an order 5'-Hbby, Hbb-bhO, Hbb-bhl, Hbb-bh2, Hbb-bh3, Hbb-bl, Hbb-b2 3') highlight organizational trends in the beta-globin complex since the two species diverged [15].
• There is a compensatory increase in synthesis of beta minor globin, resulting in a beta minor/alpha globin ratio of 0.75 in the homozygous thalassemic mouse, as compared to 0.2 in the normal homozygous diffuse mouse [1].
• Nevertheless, expression of the beta-minor globin gene in EKLF KO mice has not been assessed to date [9].
• Hexamethylenebisacetamide-mediated induction of murine erythroleukemia cells: relationship between expression of beta major and beta minor globin genes, globin mRNA synthesis and commitment to erythroid differentiation [16].

References