There has been little progress in identifying molecular events of import in renal organogenesis or in the related problem of defining the basis for kidney specific gene expression. This application proposes a program of studies whose long-term goal is to isolate genes encoding transcription factors which regulate gene expression in the kidney. Our approach utilizes a marker gene, the Tamm-Horsfall (TH) gene, that is unique to the kidney and is highly conserved in expression pattern and sequence in different mammalian species.
Our aims are to delineate cis sequences and clone transcription factors regulating TH expression in the kidney. We intend to use diverse cellular and molecular methodologies to answer this question. These approaches include: transgenic mice, retroviral infection into embryonic kidney explants, cell culture transfection, DNAse I hypersensitive site mapping, gel shift analysis, DNAse I footprinting, in vitro transcription and expression cloning for transcription factor genes. These studies will (1) lead to an understanding of how gene expression is modulated in the kidney, (2) identify proteins of importance in kidney differentiation and growth with particular emphasis on the distal nephron where THP expression occurs, and (3) possibly provide novel insights into renal disease processes due to nephron injury or abnormal development.
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