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All ETDs from UAB

2011

Hemoglobin switching

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Full-Text Articles in Medicine and Health Sciences

Piggybac Transposon Mutagenesis In Human And Mouse Stem Cells, Tingting Zhang Jan 2011

Piggybac Transposon Mutagenesis In Human And Mouse Stem Cells, Tingting Zhang

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The most common genetic diseases worldwide, £] thalassemia and Sickle Cell Anemia (SCA) result from mutations in the adult £] globin gene. One promising therapeutic method to ameliorate these diseases is to reactivate the endogenous fetal f× globin gene. I hypothesize that an erythroid mutagenic transposon system can be used to activate f× globin gene expression. To test this hypothesis three lines of genetically modified mice were generated and bred together. The first is a transgenic mouse line that contains a multicopy array of erythroid mutagenic PiggyBac (PB) transposons. The second transgenic mouse line expresses the PB transposase (TPase) from …


Hemoglobin Switching, Thalassemia And Sickle Cell Disease In Humanized Knockin Mice, Sean Mcconnell Jan 2011

Hemoglobin Switching, Thalassemia And Sickle Cell Disease In Humanized Knockin Mice, Sean Mcconnell

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In this dissertation we describe knockin mouse models for the study of human hemoglobin disorders. These knockin human globin genes, in contrast to transgenes, replace the adult mouse globin genes, remain under control of endogenous mouse globin enhancer sequences and are inherited in a manner identical to globin alleles in man. Starting with various knockin alleles composed of unique human alpha, beta and gamma globin gene sequences, we evaluate several allele combinations towards our goal of generating improved models of thalassemia and sickle cells disease. We show that humanized knockin mice complete a fetal to adult hemoglobin switch during postnatal …