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
Issue Date
2013-08-31Author
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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Show full item recordAbstract
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.
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- KU Med Center Dissertations and Theses [464]
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