NDLI: Untangling HDL quantitative trait loci on mouse chromosome 5 and identifying Scarb1 and Acads as the underlying genes.

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Untangling HDL quantitative trait loci on mouse chromosome 5 and identifying Scarb1 and Acads as the underlying genes.

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Untangling HDL quantitative trait loci on mouse chromosome 5 and identifying Scarb1 and Acads as the underlying genes.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Su, Zhiguang Leduc, Magalie S. Korstanje, Ron Paigen, Beverly
Description	Author Affiliation: Su Z ( Laboratory of Cardiovascular Research, West China Hospital, State Key Laboratory of Biotherapy, Sichuan University, Chengdu City, P.R. China.)
Abstract	Two high-density lipoprotein cholesterol quantitative trait loci (QTL), Hdlq1 at 125 Mb and Hdlq8 at 113 Mb, were previously identified on mouse distal chromosome 5. Our objective was to identify the underlying genes. We first used bioinformatics to narrow the Hdlq1 locus to 56 genes. The most likely candidate, Scarb1 (scavenger receptor B1), was supported by gene expression data consistent with knockout and transgenic mouse models. Then we confirmed Hdlq8 as an independent QTL by detecting it in an intercross between NZB and NZW (LOD = 12.7), two mouse strains that have identical genotypes for Scarb1. Haplotyping narrowed this QTL to 9 genes; the most likely candidate was Acads (acyl-coenzymeA dehydrogenase, short chain). Sequencing showed that Acads had an amino acid polymorphism, Gly94Asp, in a conserved region; Western blotting showed that protein levels were significantly different between parental strains. A previously known spontaneous deletion causes loss of ACADS activity in BALB/cBy mice. We showed that HDL levels were significantly elevated in BALB/cBy compared with BALB/c mice and that this HDL difference cosegregated with the Acads mutation. We confirmed that Hdlq1 and Hdlq8 are independent QTL on mouse chromosome 5 and demonstrated that Scarb1 and Acads are the underlying genes.
File Format	HTM / HTML
ISSN	00222275
e-ISSN	15397262
DOI	10.1194/jlr.M008110
Journal	The Journal of Lipid Research
Issue Number	9
Volume Number	51
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2010-09-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Biochemistry Acyl-coa Dehydrogenase Genetics Cholesterol, Hdl Chromosomes, Mammalian Isoenzymes Quantitative Trait Loci Scavenger Receptors, Class B Amino Acid Sequence Animals Chromosome Mapping Crosses, Genetic Genotype Haplotypes Mice Mice, Inbred Balb C Mice, Inbred Nzb Molecular Sequence Data Sequence Alignment Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Endocrinology

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