Quantitative trait locus mapping and identification of Zhx2 as a novel regulator of plasma lipid metabolism

Peter S. Gargalovic, Ayça Erbilgin, Omid Kohannim, Joanne Pagnon, Xuping Wang, Lawrence Castellani, Renee LeBoeuf, Martha L. Peterson, Brett T. Spear, Aldons J. Lusis

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Background-We previously mapped a quantitative trait locus on chromosome 15 in mice contributing to high-density lipoprotein cholesterol and triglyceride levels and now report the identification of the underlying gene. Methods and Results-We first fine-mapped the locus by studying a series of congenic strains derived from the parental strains BALB/cJ and MRL/MpJ. Analysis of gene expression and sequencing followed by transgenic complementation led to the identification of zinc fingers and homeoboxes 2 (Zhx2), a transcription factor previously implicated in the developmental regulation of α-fetoprotein. Reduced expression of the protein in BALB/cJ mice resulted in altered hepatic transcript levels for several genes involved in lipoprotein metabolism. Most notably, the Zhx2 mutation resulted in a failure to suppress expression of lipoprotein lipase, a gene normally silenced in the adult liver, and this was normalized in BALB/cJ mice carrying the Zhx2 transgene. Conclusions-We identified the gene underlying the chromosome 15 quantitative trait locus, and our results show that Zhx2 functions as a novel developmental regulator of key genes influencing lipoprotein metabolism.

Original languageEnglish
Pages (from-to)60-67
Number of pages8
JournalCirculation: Cardiovascular Genetics
Volume3
Issue number1
DOIs
StatePublished - Feb 2010

Keywords

  • Atherosclerosis
  • Genes
  • Genetics
  • Lipoproteins
  • Mapping

ASJC Scopus subject areas

  • Genetics
  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)

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