Abstract

Autosomal dominant polycystic kidney disease (ADPKD) affects l in 1,000 of the U.S. population. Previous linkage analyses have shown that 95% of the mutations affect the PKD1 gene on chromosome 16, band p13.3. The region containing the PKD1 gene has previously been mapped to a 500kb interval 3Mb from the tip of the chromosome. Twenty-three candidate genes have been identified within this region. Single-stranded conformational polymorphism analysis will be used to locate the mutations within these genes. Linkage disequilibrium studies of genetic linkage analysis will also be used to further refine the localization of the PKD 1 gene. Once the PKD1 gene has been identified, studies will be aimed at establishing the relationship between genotypes and phenotypes. A cloned gene will be used to express the PKD1 product in vitro, and to raise antibodies to the product so that its distribution of molecular interaction can be studied. Disruption of a gene on chromosome 14 in the mouse has been shown to cause a recessive polycystic kidney disease very similar to human recessive disease. We plan to study the human homolog of this gene and related genes to determine their involvement in a range of human cystic diseases of the kidney.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK040703-08
Application #
2141449
Study Section
Pathology A Study Section (PTHA)
Project Start
1989-01-01
Project End
1999-04-30
Budget Start
1995-05-01
Budget End
1996-04-30
Support Year
8
Fiscal Year
1995
Total Cost
Indirect Cost

  Institution

Name
Brigham and Women's Hospital
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Yao, Gang; Luo, Chong; Harvey, Michael et al. (2016) Disruption of polycystin-L causes hippocampal and thalamocortical hyperexcitability. Hum Mol Genet 25:448-58
Su, Xuefeng; Wu, Maoqing; Yao, Gang et al. (2015) Regulation of polycystin-1 ciliary trafficking by motifs at its C-terminus and polycystin-2 but not by cleavage at the GPS site. J Cell Sci 128:4063-73
Yao, Gang; Su, Xuefeng; Nguyen, Vy et al. (2014) Polycystin-1 regulates actin cytoskeleton organization and directional cell migration through a novel PC1-Pacsin 2-N-Wasp complex. Hum Mol Genet 23:2769-79
Yao, Gang; Luyten, Annouck; Takakura, Ayumi et al. (2013) The cytoplasmic protein Pacsin 2 in kidney development and injury repair. Kidney Int 83:426-37
Qin, Shan; Taglienti, Mary; Cai, Lei et al. (2012) c-Met and NF-ýýB-dependent overexpression of Wnt7a and -7b and Pax2 promotes cystogenesis in polycystic kidney disease. J Am Soc Nephrol 23:1309-18
Takakura, Ayumi; Nelson, Erik A; Haque, Nadeem et al. (2011) Pyrimethamine inhibits adult polycystic kidney disease by modulating STAT signaling pathways. Hum Mol Genet 20:4143-54
Luyten, Annouck; Su, Xuefeng; Gondela, Sarah et al. (2010) Aberrant regulation of planar cell polarity in polycystic kidney disease. J Am Soc Nephrol 21:1521-32
Qin, Shan; Taglienti, Mary; Nauli, Surya M et al. (2010) Failure to ubiquitinate c-Met leads to hyperactivation of mTOR signaling in a mouse model of autosomal dominant polycystic kidney disease. J Clin Invest 120:3617-28
Subramanian, Balajikarthick; Rudym, Darya; Cannizzaro, Chris et al. (2010) Tissue-engineered three-dimensional in vitro models for normal and diseased kidney. Tissue Eng Part A 16:2821-31
Takakura, Ayumi; Contrino, Leah; Zhou, Xiangzhi et al. (2009) Renal injury is a third hit promoting rapid development of adult polycystic kidney disease. Hum Mol Genet 18:2523-31

Showing the most recent 10 out of 39 publications