title: Quantitative trait locus mapping and identification of Zhx2 as a novel regulator of plasma lipid metabolism.
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.
  
  
  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 alpha-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.
authors.affiliation: Department of Medicine, Microbiology, University of California, Los Angeles, CA 90095-1679, USA.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Gargalovic
authors.forename: Ayça
authors.initials: A
authors.lastname: Erbilgin
authors.forename: Omid
authors.initials: O
authors.lastname: Kohannim
authors.forename: Joanne
authors.initials: J
authors.lastname: Pagnon
authors.forename: Xuping
authors.initials: X
authors.lastname: Wang
authors.forename: Lawrence
authors.initials: L
authors.lastname: Castellani
authors.forename: Renee
authors.initials: R
authors.lastname: LeBoeuf
authors.forename: Martha L
authors.initials: ML
authors.lastname: Peterson
authors.forename: Brett T
authors.initials: BT
authors.lastname: Spear
authors.forename: Aldons J
authors.initials: AJ
authors.lastname: Lusis
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D005260:Female; D020869:Gene Expression Profiling; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics*; D050356:Lipid Metabolism / Q000235:genetics*; D008055:Lipids / Q000097:blood*; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism; D008074:Lipoproteins / Q000235:genetics; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009154:Mutation; D040641:Quantitative Trait Loci; D012333:RNA, Messenger / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000235:genetics / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; C524979:Hyplip2 protein, mouse; D008055:Lipids; D008074:Lipoproteins; D012333:RNA, Messenger; C481543:Zhx2 protein, mouse; D000509:alpha-Fetoproteins; D008071:Lipoprotein Lipase