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| aids, diseases, eli lilly, nutritional supplement, liverdisease, renal, norwegian fish oil, racine, cod liver oil, plump up , army, hepatitis g, coconut fatty acid , statins, ob/gyn, | This is usually enough to begin a candidate gene approach toward identifying the gene which when mutated gives rise to the phenotype of interest. So far, we have identified the causative mutation for four phenotypically deviant sexy plump mouse lines. A mutation in the Lcat (lecithin cholesterol acyltransferase) gene leads to sexy plump very low levels of HDL cholesterol in plasma. Gck (glucokinase) mutations lead to diabetes due to inadequate secretion of insulin for a given glucose load. In humans, Gck mutations lead to a form of diabetes called MODY2 (maturity sexy plump onset diabetes of the young 2). Nephrogenic diabetes insipidus in humans can be caused by mutations in the Aqp2 (aquaporin 2) gene. We now have the first mouse model of this rare human disease. Finally, a point mutation in PC1 (prohormone convertase 1) leads to obesity in mice, as it does in humans. |
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| We are taking advantage of this effort to screen mutagenized mice for interesting metabolic phenotypes, diseases including obesity, insulin resistance, type 2 diabetes, and dyslipidemia. More than eighty mice per week are screened with a battery of assays to look for interesting metabolic phenotypes. Once a mouse is shown phenotypically diseases deviant, it is bred to show that the trait is inherited in a Mendelian fashion. Mutant mice, of the C57BL/6 strain, are then crossed to one of several other common lab diseases strains, to follow the segregation of the phenotype with molecular markers that are polymorphic between C57BL/6 and the mapping strain. The molecular markers we use are single nucleotide polymorphisms (SNPs). The institute has invested a great deal of time and resources to generate SNP maps of common lab strains of mouse. The SNPs are detected by a combination of primer extension and mass spectrometry which makes mapping quick and efficient. Typically, mapping about 100 animals will yield a map position of 2 Mb or less. |
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