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    SPLICING ERROR IN GATA1 AFFECTS ERYTHROPOIESIS IN THE XPNA MOUSE (X-LINKED PRE- AND NEONATAL ANEMIA) WITH SUGGESTION OF A NOVEL COMPENSATORY ERYTHROID TRANSCRIPTION FACTOR

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    Miller_ku_0099M_12948_DATA_1.pdf (1.257Mb)
    Issue Date
    2013-08-31
    Author
    Miller, Kyle Lamar
    Publisher
    University of Kansas
    Format
    34 pages
    Type
    Thesis
    Degree Level
    M.S.
    Discipline
    Preventive Medicine and Public Health
    Rights
    This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
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    Abstract
    A novel mutant mouse called X-linked pre- and neonatal anemia (gene symbol, Xpna) results in a transient, neonatal anemia which is resolved by 3 weeks of age in Xpna females. Adult Xpna females exhibit hypoplastic bone marrow with red cell aplasia and splenomegaly showing extramedullary erythropoiesis and megakaryocytosis. We identified a splicing defect derived from a single nucleotide change 5 base pairs downstream of Exon 1 in Gata1. The Xpna Gata1 gene produces a transcript, which includes alternative Exon 1Eb/c, known not to induce erythropoiesis. X-chromosome inactivation leads to two populations of hematopoietic cells in Xpna females, one of which expresses Xpna Gata1 mRNA. An X-chromosome-associated erythroid genetic marker (Pgk1, phosphoglycerate kinase-1) indicates reticulocytes are derived from erythropoietic cells expressing the Xpna Gata1 transcript. These data strongly suggest compensatory gene expression allowing for the generation of erythrocytes despite the lack of GATA-1 production. The Xpna mouse could, therefore, lead to the identification of novel erythropoietic factors.
    URI
    http://hdl.handle.net/1808/12271
    Collections
    • KU Med Center Dissertations and Theses [464]
    • Theses [3827]

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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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