Abstract/Details

Novel involvement of nuclear hormone receptors in autosomal dominant polycystic kidney disease


2006 2006

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Abstract (summary)

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a systemic disorder that affects approximately 1 in 1000 individuals. It is caused by mutations of PKD1 and PKD2. Murine gene targeting studies have shown that these genes have an essential role in development, with homozygous inactivation resulting in pre-natal lethality. Among the noted abnormalities seen in Pkd1-/- mice are a variety of cardiovascular defects, diffuse renal cysts, and placental abnormalities, which are responsible for Pkd1-/- fetal demise. In these studies, our goal was to better understand the underlying transcriptional alterations that result in these developmental abnormalities. This was done by conducting microarray analysis of these affected tissues at multiple timepoints in development. Microarray analysis of Pkd1-/- tissues showed upregulation of a set of apolipoproteins and apolipoprotein-related transcripts. These transcriptional changes were validated using a variety of independent methods and were found to be associated with increased amounts of apolipoproteins in amniotic fluid. Similar abnormalities were observed in Pkd2-/- placentae and in kidneys of Pkd1cond/-; Meox2cre/+ mice. Increased HNF-4α activity and decreased transcription of COUP-TFII were also observed. These findings suggest a role for polycystin-1 and -2 in the regulation of nuclear hormone receptors and implicate the latter in the pathogenesis of disease.

Indexing (details)


Subject
Genetics;
Pathology
Classification
0369: Genetics
0571: Pathology
Identifier / keyword
Health and environmental sciences; Biological sciences; Apolipoproteins; Autosomal dominant polycystic kidney disease; Kidney disease; Nuclear hormone receptors
Title
Novel involvement of nuclear hormone receptors in autosomal dominant polycystic kidney disease
Author
Allen, Erica Lynn
Number of pages
94
Publication year
2006
Degree date
2006
School code
0098
Source
DAI-B 66/12, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
0542429144, 9780542429149
Advisor
Germino, Gregory
University/institution
The Johns Hopkins University
University location
United States -- Maryland
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3197104
ProQuest document ID
305318408
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/305318408
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