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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK044921-05
Application #
2144176
Study Section
Pathology A Study Section (PTHA)
Project Start
1992-05-01
Project End
1997-04-30
Budget Start
1995-05-01
Budget End
1996-04-30
Support Year
5
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02215
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Yu, H; Papa, F; Sukhatme, V P (1994) Bovine and rodent tamm-horsfall protein (THP) genes: cloning, structural analysis, and promoter identification. Gene Expr 4:63-75
Drummond, I A; Rupprecht, H D; Rohwer-Nutter, P et al. (1994) DNA recognition by splicing variants of the Wilms' tumor suppressor, WT1. Mol Cell Biol 14:3800-9

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