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EXPRESSION MICROARRAY ANALYSIS OF RENAL DEVELOPMENT AND HUMAN RENAL DISEASE

SCHWAB, KRISTOPHER R
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1157651859

Abstract Details

2006, PhD, University of Cincinnati, Medicine : Molecular and Developmental Biology.
Renal morphogenesis involves the reciprocal inductive interactions between the ureteric bud and metanephric mesenchyme forming the collecting ducts and nephrons within adult kidney. We applied microarray technology to the study of renal morphogenesis in order to better understand the molecular mechanisms underlying development. Additionally, the techniques employed in the expression analysis of the embryonic kidney were extended to the study of renal disease. Embryonic kidneys representing different stages of renal development were analyzed using expression microarrays. Renal developmental analysis revealed many novel genes and genetic pathways involved in renal development. In addition, the normal renal development data provides a baseline for the analysis of gene targeted mice possessing disruptions in renal morphogenesis. Microarray analysis was also performed on the Hoxa11/Hoxd11 compound null renal defect throughout renal development. In conclusion, these microarray studies greatly advance our knowledge of gene expression within the normal renal morphogenesis and identify possible downstream candidate genes regulated by the Hox11 genes. Wnt signaling is crucial for normal renal morphogenesis. In Drosophila, the pygopus gene encodes a transcriptional co-activator required for canonical Wnt signaling. The targeted deletion of the mammalian orthologs of pygopus, Pygo1 and Pygo2, in mice was investigated in renal development. A disruption in ureteric number tip and morphology was identified in Pygo1/Pygo2 compound null kidneys. Additionally, canonical Wnt signaling as measure by the Bat-gal transgene is reduced within the ureteric compartment in Pygo1/Pygo2 null kidneys. Overall, these experiments suggest that Pygo function is required for activation of canonical Wnt signaling in the ureteric compartment of the developing kidney. Focal segmental glomerulosclerosis (FSGS) is characterized by the segmental scarring of the glomerulus, ultimately resulting loss of nephron function. To understand the molecular pathogenesis of this disease, gene expression analysis was performed on FSGS patient kidney biopsies and compared to normal kidney tissue. Hundreds of genes were identified significantly changed with in the FSGS patient groups. Furthermore, gene expression changes were identified in subsets of patients possessing different clinical manifestations of FSGS. In conclusion, the molecular analysis of gene expression in the FSGS kidney provides a better understanding of expression changes during renal disease.
Dr. S. Potter (Advisor)
264 p.
microarray; Wnt signaling; metanephros; kidney development; focal segmental glomerulosclerosis; Hox genes; gene knockout mice

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Citations

  • SCHWAB, K. R. (2006). EXPRESSION MICROARRAY ANALYSIS OF RENAL DEVELOPMENT AND HUMAN RENAL DISEASE [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1157651859

    APA Style (7th edition)

  • SCHWAB, KRISTOPHER. EXPRESSION MICROARRAY ANALYSIS OF RENAL DEVELOPMENT AND HUMAN RENAL DISEASE. 2006. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1157651859.

    MLA Style (8th edition)

  • SCHWAB, KRISTOPHER. "EXPRESSION MICROARRAY ANALYSIS OF RENAL DEVELOPMENT AND HUMAN RENAL DISEASE." Doctoral dissertation, University of Cincinnati, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1157651859

    Chicago Manual of Style (17th edition)

ucin1157651859
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© 2006, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.