Quantitative Trait Locus Mapping of Genetic Modifiers of Metabolic Syndrome and Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice
| Autor: | Sara B. Seidelmann, Carl De Luca, Rudolph L. Leibel, Jan L. Breslow, Carrie L. Welch, Alan R. Tall |
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| Rok vydání: | 2005 |
| Předmět: |
Genetic Markers
Male medicine.medical_specialty Arteriosclerosis Quantitative Trait Loci Mice Inbred Strains Locus (genetics) Quantitative trait locus Biology Chromosomes Article Mice Inbred strain Gene mapping Internal medicine medicine Animals Crosses Genetic Metabolic Syndrome Genetics Chromosome Mapping medicine.disease Null allele Mice Inbred C57BL Phenotype Endocrinology Receptors LDL Genetic marker LDL receptor Female Metabolic syndrome Cardiology and Cardiovascular Medicine |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 25:204-210 |
| ISSN: | 1524-4636 1079-5642 |
| DOI: | 10.1161/01.atv.0000149146.32385.1b |
| Popis: | Objective— The purpose of this study was to examine genetic factors responsible for metabolic syndrome and atherosclerosis in a setting of low-density lipoprotein (LDL) receptor deficiency in a cross between C57BL/6J (B6) and PERA/Ei (PERA) inbred mouse strains. Methods and Results— Comparison of metabolic phenotypes in B6 and PERA strains revealed the PERA genetic background to be dramatically more susceptible to hyperleptinemia, hyperglycemia, hypertriglyceridemia, elevated insulin levels, and body fat increase than the B6 background. To facilitate genetic analysis, metabolic syndrome-related traits and atherosclerotic lesion area were measured in 167 [(PERA×B6.129S7- Ldlr tm1Her )×B6.129S7- Ldlr tm1Her ]N2 male and female backcross mice that were homozygous for the Ldlr null allele. Quantitative trait locus analysis was performed using 153 polymorphic microsatellite markers spanning the genome. On chromosome 4, we identified a locus influencing plasma triglyceride, insulin, and leptin concentrations, body weight, and atherosclerosis. Several other genetic loci were identified with separate effects on plasma insulin, body weight, high-density lipoprotein cholesterol, and atherosclerosis. Conclusions— The PERA strain is highly susceptible to the development of metabolic syndrome after feeding a Western-type diet. This susceptibility is due, in part, to a locus on murine chromosome 4 in which PERA alleles predispose to adiposity, increased insulin, and accelerated atherogenesis in the absence of marked hyperlipidemia. |
| Databáze: | OpenAIRE |
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