Experiment
Previously identified obesity QTLs Mob5 and Mob6 on mouse Chromosome 2 were further examined using congenic line analysis. CAST/EiJ-derived DNA spanning 84 Mb - 180 Mb (D2Mit9 to D2Mit50) on chromosome 2 was introgressed onto a C57BL/6J genetic background to create the Mob5 congenic line. T
he Mob6 congenic line carries CAST/EiJ-derived DNA from 67 Mb - 162 Mb (D2Mit14a to D2Mit457) on a C57BL/6J background. Parental strain CAST/EiJ is resistant to obesity whereas C57BL/6J is obesity-prone. Congenic animals were bred to C57BL/6J-Ldlrtm1Her to predispose to atherosclerosis and defective glucose homeostasis.
B6.CAST-Ldlrtm1Her Mob6 animals display 2- to 3-fold decreased aortic root lesion, decreased plasma cholesterol, and increased food efficiency compared to C57BL/6J-Ldlrtm1Her controls. (Decreased plasma cholesterol includes HDL, LDL, VLDL, and unesterified cholesterol.) When fed a Western diet, B6.CAST-Ldlrtm1Her Mob6 exhibit decreased obesity and improved glucose tolerance compared to C57BL/6J-Ldlrtm1Her controls. B6.CAST-Mob6 animals are also less obese on a Western diet.
B6.CAST-Mob5 animals display improved glucose clearance and decreased plasma cholesterol compared to C57BL/6J-Ldlrtm1Her controls. These animals also display increasedfood consumption, decreased plasma triglycerides, decreased free fatty acids, and decreased plasma glucose on a Western diet. B6.CAST-Ldlrtm1Her Mob5 animals have decreased plasma total cholesterol as well as decreased HDL, LDL, VLDL, and unesterifiedcholesterol. Both B6.CAST-Ldlrtm1Her Mob5 and B6.CAST-Mob5 animals are more resistant to insulin-stimulated glucose uptake compared to C57BL/6J-Ldlrtm1Her controls.