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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/25729

Title: Investigating the Roles of Homeobox Containing Transcription Factors Iroquois 3/5 in Mammalian Heart Development and Electrophysiology
Authors: Kim, Jieun
Advisor: Hui, Chi-chung
Department: Molecular and Medical Genetics
Keywords: Iroquois
heart development
cardiac electrophysiology
cardiac transcription factor
Issue Date: 6-Jan-2011
Abstract: Iroquois homeobox (Irx) family members, a group of highly conserved homeodomain containing transcription factors, are involved in the patterning and the proper functions of vertebrate organs. They can act as transcriptional activators or repressors in a context-dependent manner. Preliminary data indicated that Irx3 and Irx5 are functionally redundant during cardiac morphogenesis, and they physically interact with other cardiac transcription factors. At E14.5, outflow tract septation failure and ventricular septation failure were observed in Irx3/5DKO mouse hearts. Loss of Irx3/5 in neural crest and endothelial cell lineages led to outflow tract septation failure and ventricular septal defect. In adult mice, Irx3 is expressed in the atrioventricular conduction system, and loss of Irx3 leads to slower ventricular conduction velocity. qRT-PCR analysis and immunofluorescence staining revealed that the expression of gap junction proteins, Cx40 and Cx43, are affected by the loss of Irx3. Over-expression of Irx3 and a dominant repressor form of Irx3, Irx3-EnR, resulted in Cx40 upregulation, indicating that Irx3 acts as an indirect positive regulator of Cx40. Irx3-EnR over-expression in vivo resulted in postnatal onset of atrial enlargement, ventricular hypertrophy, and conduction failure. Taken together, this study demonstrates the significance of Irx3/5 in both cardiovascular development and cardiac electrophysiology.
URI: http://hdl.handle.net/1807/25729
Appears in Collections:Master
Department of Molecular Genetics - Master theses

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