Quantitative trait locus mapping and identification of Zhx2 as a novel regulator of plasma lipid metabolism.
نویسندگان
چکیده
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 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.
منابع مشابه
Identification and characterization of a novel murine allele of Tmprss6.
Mutagenesis screens can establish mouse models of utility for the study of critical biological processes such as iron metabolism. Such screens can produce mutations in novel genes or establish novel alleles of known genes, both of which can be useful tools for study. In order to identify genes of relevance to hematologic as well as other phenotypes, we performed N-ethyl-N-nitrosourea mutagenesi...
متن کاملIdentification of Quantitative Trait Loci That Determine Plasma Total-Cholesterol and Triglyceride Concentrations in DDD/Sgn and C57BL/6J Inbred Mice
DDD/Sgn mice have significantly higher plasma lipid concentrations than C57BL/6J mice. In the present study, we performed quantitative trait loci (QTL) mapping for plasma total-cholesterol (CHO) and triglyceride (TG) concentrations in reciprocal F2 male intercross populations between the two strains. By single-QTL scans, we identified four significant QTL on chromosomes (Chrs) 1, 5, 17, and 19 ...
متن کاملIdentification and Mapping of Quantitative Trait Loci Associated with Salinity Tolerance in Rice (Oryza Sativa) Using SSR Markers
Salinity stress is one of the most widespread soil problems next to drought, in rice growing areas. ReducingSodium (Na+), while maintaining Potassium (K+) uptake in rice are traits that would aid in salinity tolerance.Therefore, the identification of quantitative trait loci (QTLs) associated with those for Na+ and K+uptake, will enable breeders to use marker-assisted selection...
متن کاملFunctional Analysis of the TRIB1 Associated Locus Linked to Plasma Triglycerides and Coronary Artery Disease
BACKGROUND The TRIB1 locus has been linked to hepatic triglyceride metabolism in mice and to plasma triglycerides and coronary artery disease in humans. The lipid-associated single nucleotide polymorphisms (SNPs), identified by genome-wide association studies, are located ≈30 kb downstream from TRIB1, suggesting complex regulatory effects on genes or pathways relevant to hepatic triglyceride me...
متن کاملQTL mapping of heading date and plant height in Barley cross “Azumamugi”דKanto Nakate Gold
To identify quantitative trait loci (QTLs) controlling heading date and plant height, ninety nine F13 recombinant inbred lines (RILs) derived from barley cultivars Azumamugi × Kanto Nakate Gold cross were evaluated. The field trails were conducted at randomized complete block design with two and three replications in 2004 and 2005, respectively. Significant differences and transgrassive segrega...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Circulation. Cardiovascular genetics
دوره 3 1 شماره
صفحات -
تاریخ انتشار 2010