Loss of polycystin-1 or polycystin-2 results in dysregulated apolipoprotein expression in murine tissues via alterations in nuclear hormone receptors

Erica Allen, Klaus B. Piontek, Elizabeth Garrett-Mayer, Miguel Garcia-Gonzalez, Kerry Lee Gorelick, Gregory G. Germino

Research output: Contribution to journalArticle

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations of PKD1 and PKD2. Murine gene targeting studies have shown that these genes play an essential role in development, with homozygous inactivation resulting in embryonic lethality. Recently, Pkd1-/- lethality has been linked to placental insufficiency. In this study, the placenta was used as a model to identify factors involved in these developmental abnormalities. Microarray analysis of Pkd1-/- placentae showed upregulation of a set of apolipoprotein-related genes. These changes were validated and were found to be associated with increased quantities of apolipoproteins in the amniotic fluid. Increased apolipoprotein gene expression was also observed in Pkd2-/- placentae and in cystic kidneys of Pkd1cond/-; Meox2cre/+ mice. Using chromatin immunoprecipitation assays, we determined that the activity of HNF-4α, a major regulator of apolipoprotein gene expression, was also increased in these organs. These findings suggest a potential role for dysregulation of nuclear hormone receptors in the pathogenesis of ADPKD.

Original languageEnglish (US)
Pages (from-to)11-21
Number of pages11
JournalHuman Molecular Genetics
Volume15
Issue number1
DOIs
StatePublished - Jan 1 2006

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Apolipoproteins
Cytoplasmic and Nuclear Receptors
Placenta
Autosomal Dominant Polycystic Kidney
Placental Insufficiency
Cystic Kidney Diseases
Gene Expression
Gene Targeting
Chromatin Immunoprecipitation
Essential Genes
Amniotic Fluid
Regulator Genes
Microarray Analysis
Up-Regulation
Mutation
polycystic kidney disease 1 protein
polycystic kidney disease 2 protein
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Loss of polycystin-1 or polycystin-2 results in dysregulated apolipoprotein expression in murine tissues via alterations in nuclear hormone receptors. / Allen, Erica; Piontek, Klaus B.; Garrett-Mayer, Elizabeth; Garcia-Gonzalez, Miguel; Gorelick, Kerry Lee; Germino, Gregory G.

In: Human Molecular Genetics, Vol. 15, No. 1, 01.01.2006, p. 11-21.

Research output: Contribution to journalArticle

Allen, Erica ; Piontek, Klaus B. ; Garrett-Mayer, Elizabeth ; Garcia-Gonzalez, Miguel ; Gorelick, Kerry Lee ; Germino, Gregory G. / Loss of polycystin-1 or polycystin-2 results in dysregulated apolipoprotein expression in murine tissues via alterations in nuclear hormone receptors. In: Human Molecular Genetics. 2006 ; Vol. 15, No. 1. pp. 11-21.
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