International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


ORAL PRESENTATION

THURSDAY OCTOBER 21

2.15pm – 2.30pm

ESTIMATING THE CONTRIBUTION OF GENETIC, DIET AND GENDER EFFECTS TO THE PHENOTYPIC VARIATION OBSERVED IN METABOLIC SYNDROME-RELATED TRAITS BETWEEN A/J AND C57BL/6J MICE

Sinasac DS, Nadeau JH

Case Western Reserve University, Cleveland, United States

Metabolic syndrome (MetS) refers to a constellation of cardiovascular risk factors that include obesity, hypertension, dyslipidemia and altered glucose homeostasis leading to diabetes.  Male C57BL/6J mice fed a high fat/high sucrose (HF/HS) diet are a model of MetS.  To evaluate the contribution of genetic background, diet and gender on the MetS phenotype in this model, 21 MetS-related traits were examined in male and female A/J and C57BL/6J.  At 5 weeks of age, 30 mice per group were fed either the HF/HS or maintenance diet for 16 weeks.  After 15 weeks, a fasted IPGTT was performed.  At 16 weeks, body weight/length measures, blood and liver were collected following a fast.  Plasma ALT, AST, cholesterol, glucose, insulin, NEFA and triglycerides as well as liver weight and triglyceride content were measured.  Data were analyzed using a factorial ANOVA design with planned comparison tests per trait and an experiment-wide, modified Bonferroni correction was applied.  Fourteen traits showed significant background effects, 17 significant diet effects, and 16 significant gender effects.  Interactions between factors were also noted for 13 traits.  Comparing A/J and C57BL/6J on the HF/HS diet, males showed significant differences in 12 traits, whereas females showed difference in only six.  These results indicate that the genetic differences between A/J and C57BL/6J, when exacerbated by the HF/HS diet, explains a substantial portion of the variation observed in a subset of MetS-related traits in males.  Genetic mapping studies are currently underway to examine these traits in the newly generated B6-ChrA chromosome substitution strain panel of mice.

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