The transcription factor Miz-1 is required for embryonic and stress-induced erythropoiesis but dispensable for adult erythropoiesis.

Myc-interacting zinc finger protein 1 (Miz-1) is a BTB/POZ domain transcription factor that regulates complex processes such as proliferation and apoptosis. Constitutively Miz-1-deficient animals arrest embryonic development at E14.5 due to severe anemia and fetal liver cells lacking Miz-1 show a high cell death rate and a significant reduction of mature Ter119(+)ckit(-) or Ter119(+)CD71(-/low) cells.

Growth factor independence 1b (gfi1b) is important for the maturation of erythroid cells and the regulation of embryonic globin expression.

Growth factor independence 1b (GFI1B) is a DNA binding repressor of transcription with vital functions in hematopoiesis. Gfi1b-null embryos die at midgestation very likely due to defects in erythro- and megakaryopoiesis. To analyze the full functionality of Gfi1b, we used conditionally deficient mice that harbor floxed Gfi1b alleles and inducible (Mx-Cre, Cre-ERT) or erythroid specific (EpoR-Cre) Cre expressing transgenes.

Evidence for a novel mechanism independent of myocardial iron in β-thalassemia cardiac pathogenesis.

Human β-thalassemia major is one of the most prevalent genetic diseases characterized by decrease/absence of β-globin chain production with reduction of erythrocyte number. The main cause of death of treated β-thalassemia major patients with chronic blood transfusion is early cardiac complications that have been attributed to secondary iron overload despite optimal chelation. Herein, we investigated pathophysiological mechanisms of cardiovascular dysfunction in a severe murine model of β-thalassemia from 6 to 15-months of age in the absence of confounding effects related to transfusion.

Vascular endothelial dysfunction in β-thalassemia occurs despite increased eNOS expression and preserved vascular smooth muscle cell reactivity to NO.

Aims: The hereditary β-thalassemia major condition requires regular lifelong blood transfusions. Transfusion-related iron overloading has been associated with the onset of cardiovascular complications, including cardiac dysfunction and vascular anomalies. By using an untransfused murine model of β-thalassemia major, we tested the hypothesis that vascular endothelial dysfunction, alterations of arterial structure and of its mechanical properties would occur despite the absence of treatments.

Kruppel-like factor 1 (KLF1), KLF2, and Myc control a regulatory network essential for embryonic erythropoiesis.

The Krüppel-like factor 1 (KLF1) and KLF2 positively regulate embryonic β-globin expression and have additional overlapping roles in embryonic (primitive) erythropoiesis. KLF1(-/-) KLF2(-/-) double knockout mice are anemic at embryonic day 10.5 (E10.

EKLF and KLF2 have compensatory roles in embryonic beta-globin gene expression and primitive erythropoiesis.

The Krüppel-like C2/H2 zinc finger transcription factors (KLFs) control development and differentiation. Erythroid Krüppel-like factor (EKLF or KLF1) regulates adult beta-globin gene expression and is necessary for normal definitive erythropoiesis. KLF2 is required for normal embryonic Ey- and betah1-, but not adult betaglobin, gene expression in mice.

The beta-thalassemia mutation/haplotype distribution in the moroccan population.

The present study compiles the results of our own research and of a prior study on beta-thalassemia (thal) in Morocco, comprising a total of 187 beta-thalassemic chromosomes. Six major mutations: (beta0) codon 39 (C --> T), (beta+) IVS-I-6 (T --> C), (beta0) frameshift codon (FSC) 6 (-A), (beta0) FSC 8 (-AA), (beta0) IVS-I-1 (G --> A) and (beta+) -29 (A --> G) account for 75.7% of the independent chromosomes studied.

Spectrum of beta thalassemia mutations and HbF levels in the heterozygous Moroccan population.

A comprehensive hematological and molecular analysis of 57 beta thalassemic heterozygotes, 28 homozygotes, 18 double heterozygotes, 3 compound heterozygotes beta thal/beta S and one compound heterozygote beta thal/Hb Newcastle, in 46 Moroccan families with at least one beta thalassemia patient is reported. Six major mutations: beta(0)39 (C-->T), beta(0)FsCD8(-AA), beta(+)IVS1,nt6 (T-->C) and beta(0)IVS1,nt1 (G-->A), beta(0)FsCD6 (-A) and beta(+)-29 (A-->G) cap site account for 75% of the 86 independent beta thal chromosomes studied. For the first time, an extensive mutation/haplotype study has been performed on the Moroccan population, and data are consistent with the geographical location of the country and historical links with both the Mediterranean and the Sub-Saharan Africa communities.