title: The transcription factor Miz-1 is required for embryonic and stress-induced erythropoiesis but dispensable for adult erythropoiesis.
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.
authors.affiliation: Institut de Recherches Cliniques de Montréal, IRCM Montréal, Canada ; Institut für Biochemie, Friedrich Schiller Universität Jena Jena, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Kosan
authors.affiliation: Institut de Recherches Cliniques de Montréal, IRCM Montréal, Canada ; Division of Experimental Medicine, McGill University Montreal, Canada.
authors.forename: Marissa
authors.initials: M
authors.lastname: Rashkovan
authors.affiliation: Institut de Recherches Cliniques de Montréal, IRCM Montréal, Canada ; Division of Experimental Medicine, McGill University Montreal, Canada.
authors.forename: Julie
authors.initials: J
authors.lastname: Ross
authors.affiliation: Institut für Biochemie, Friedrich Schiller Universität Jena Jena, Germany.
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Schaffer
authors.affiliation: Institut de Recherches Cliniques de Montréal, IRCM Montréal, Canada.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Saba
authors.affiliation: Institut de Recherches Cliniques de Montréal, IRCM Montréal, Canada.
authors.forename: Wafaa
authors.initials: W
authors.lastname: Lemsaddek
authors.affiliation: 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.
authors.forename: Marie
authors.initials: M
authors.lastname: Trudel
authors.affiliation: 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.
authors.forename: Tarik
authors.initials: T
authors.lastname: Möröy
keywords: BTB/POZ domain; Epo; Miz-1; STAT5; erythropoiesis; transcription factor