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Kosan C, Rashkovan M, Ross J, et al. The transcription factor Miz-1 is required for embryonic and stress-induced erythropoiesis but dispensable for adult erythropoiesis. Am J Blood Res. 2014;4(1):7-19
Kosan, C., Rashkovan, M., Ross, J., Schaffer, A. M., Saba, I., Lemsaddek, W., Trudel, M., & Möröy, T. (2014). The transcription factor Miz-1 is required for embryonic and stress-induced erythropoiesis but dispensable for adult erythropoiesis. American journal of blood research, 4(1), 7-19.
Kosan, Christian, et al. "The transcription factor Miz-1 is required for embryonic and stress-induced erythropoiesis but dispensable for adult erythropoiesis." American journal of blood research vol. 4,1 (2014): 7-19.
Kosan C, Rashkovan M, Ross J, Schaffer AM, Saba I, Lemsaddek W, Trudel M, Möröy T. The transcription factor Miz-1 is required for embryonic and stress-induced erythropoiesis but dispensable for adult erythropoiesis. Am J Blood Res. 2014 Sep 05;4(1):7-19. eCollection 2014. PMID: 25232500; PMCID: PMC4165114.
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Am J Blood Res. 2014 Sep 05;4(1):7-19. eCollection 2014.

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

American journal of blood research

Christian Kosan, Marissa Rashkovan, Julie Ross, Anna-Maria Schaffer, Ingrid Saba, Wafaa Lemsaddek, Marie Trudel, Tarik Möröy

Affiliations

  1. Institut de Recherches Cliniques de Montréal, IRCM Montréal, Canada ; Institut für Biochemie, Friedrich Schiller Universität Jena Jena, Germany.
  2. Institut de Recherches Cliniques de Montréal, IRCM Montréal, Canada ; Division of Experimental Medicine, McGill University Montreal, Canada.
  3. Institut für Biochemie, Friedrich Schiller Universität Jena Jena, Germany.
  4. Institut de Recherches Cliniques de Montréal, IRCM Montréal, Canada.
  5. Institut de Recherches Cliniques de Montréal, IRCM Montréal, Canada ; Division of Experimental Medicine, McGill University Montreal, Canada ; Département de Médecine Université de Montréal Montréal, Canada.
  6. Institut de Recherches Cliniques de Montréal, IRCM Montréal, Canada ; Division of Experimental Medicine, McGill University Montreal, Canada ; Département de Microbiologie, Infectiologie et Immunologie Montréal, Canada.

PMID: 25232500 PMCID: PMC4165114

Abstract

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. Consistently, the numbers of BFU-Es and CFU-Es were severely reduced in colony forming assays. Mice with conditional Miz-1 alleles deleted around E14.5 were born at expected ratios, but had reduced numbers of erythrocytes, and showed an increase in reticulocytes and Macro-RBCs in the peripheral blood. When challenged with the hemolytic agent phenylhydrazine (PHZ), Miz-1 deficient mice responded with a severe anemia after 4 days of treatment, but showed a delay in the recovery from this anemia with regard to RBC counts, hematocrit and hemoglobin levels compared to controls. In addition, an accumulation of immature CD71(+)Ter119(+) cells occurred in the bone marrow and spleen of mice lacking a functional Miz-1. We conclude from our studies that Miz-1 is important for erythroid differentiation and development. Moreover, Miz-1 is necessary to maintain a peripheral red blood cell homeostasis in particular in response to hemolysis after oxidative stress.

Keywords: BTB/POZ domain; Epo; Miz-1; STAT5; erythropoiesis; transcription factor

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