Genetic loci controlling body fat, lipoprotein metabolism, and insulin levels in a multifactorial mouse model
| Autor: | Janis S. Fisler, Ping Zi Wen, Margarete Mehrabian, Aldons J. Lusis, Richard C. Davis |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Leptin
Male medicine.medical_specialty Candidate gene Lipoproteins medicine.medical_treatment Mice Inbred Strains Receptors Cell Surface Locus (genetics) Quantitative trait locus Biology Mice Quantitative Trait Heritable Internal medicine Diabetes mellitus medicine Animals Insulin Obesity Chromosome Mapping Proteins General Medicine medicine.disease Endocrinology Adipose Tissue Diabetes Mellitus Type 2 Receptors Leptin Female Insulin Resistance Carrier Proteins Research Article Lipoprotein |
| Zdroj: | Journal of Clinical Investigation. 101:2485-2496 |
| ISSN: | 0021-9738 |
| DOI: | 10.1172/jci1748 |
| Popis: | We analyzed the inheritance of body fat, leptin levels, plasma lipoprotein levels, insulin levels, and related traits in an intercross between inbred mouse strains CAST/Ei and C57BL/6J. CAST/Ei mice are unusually lean, with only approximately 8% of body weight as fat, whereas C57BL/6J mice have approximately 18% body fat. Quantitative trait locus analysis using > 200 F2 mice revealed highly significant loci (lod scores > 4.3) on chromosomes 2 (three separate loci) and 9 that contribute to mouse fat-pad mass for mice on a high-fat diet. Some loci also influenced plasma lipoprotein levels and insulin levels either on chow or high-fat diets. Two loci for body fat and lipoprotein levels (on central and distal chromosome 2) coincided with a locus having strong effects on hepatic lipase activity, an activity associated with visceral obesity and lipoprotein levels in humans. A locus contributing to plasma leptin levels (lod score 5.3) but not obesity was identified on chromosome 4, near the leptin receptor gene. These data identify candidate regions and candidate genes for studies of human obesity and diabetes, and suggest obesity is highly complex in terms of the number of genetic factors involved. Finally, they support the existence of specific genetic interactions between body fat, insulin metabolism, and lipoprotein metabolism. |
| Databáze: | OpenAIRE |
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