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Genetic Resistance to Diet-Induced Obesity in Mice

Burrage, Lindsay
http://rave.ohiolink.edu/etdc/view?acc_num=case1151680415

Abstract Details

2006, Doctor of Philosophy, Case Western Reserve University, Genetics.
Obesity is a major public health concern in the 21st century. Approximately one-third of U.S. adults are obese, with the prevalence of obesity and related conditions like hypercholesterolemia, hypertension, and diabetes mellitus, rising at an alarming rate. Although hereditary factors are known to influence obesity, genetic studies of human obesity are complicated by numerous environmental factors such as diet and activity level that also influence body weight. An alternative approach using inbred strains of mice which differ in their susceptibility to high-fat, diet-induced obesity, can be useful for dissecting the genetics of this highly complex trait. To investigate the genetics of high-fat, diet-induced obesity in the obesity susceptible C57BL/6J inbred strain and obesity resistant A/J inbred strain, we used the B6-Chr chromosome substitution strains (CSSs), a panel of inbred strains with individual A/J-derived chromosomes substituted onto the C57BL/6J genetic background. A CSS body weight survey identified 13 A/J chromosomes that reproducibly confer resistance to high-fat, diet-induced obesity, suggesting that at least 13 obesity resistance genes were detected. To determine the number and location of resistance genes on A/J chromosomes, intercross progeny derived from each CSS were analyzed. The intercross studies detected resistance QTLs on only three A/J chromosomes and surprisingly detected obesity promoting QTLs on two A/J chromosomes. In addition, more detailed investigation of obesity resistance on A/J chromosome 6 with congenic strains derived from the B6-Chr 6Astrain revealed evidence for at least three genes influencing obesity resistance. Collectively, our studies lend support to the theory that genetic resistance to high-fat, diet-induced obesity in our model is complex, even when narrowing our studies from the whole genome to a single chromosome level. Furthermore, phenotyping studies of B6-Chr 6A and a congenic strain derived from it also revealed resistance to several metabolic syndrome phenotypes in addition to obesity. Thus, these CSSs and congenic strains derived from them will enable the genetic dissection of obesity and metabolic syndrome, and simultaneous genetic and phenotypic studies using these strains will lead to the discovery of many obesity resistance genes and possibly novel therapeutic targets for obesity.
Joseph Nadeau (Advisor)
Biology, Genetics
C57BL/6J; QTL; OBESITY; B6-CHR; CHROMOSOME; B6-CHR 6A; CSS

Recommended Citations

Citations

  • Burrage, L. (2006). Genetic Resistance to Diet-Induced Obesity in Mice [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1151680415

    APA Style (7th edition)

  • Burrage, Lindsay. Genetic Resistance to Diet-Induced Obesity in Mice. 2006. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1151680415.

    MLA Style (8th edition)

  • Burrage, Lindsay. "Genetic Resistance to Diet-Induced Obesity in Mice." Doctoral dissertation, Case Western Reserve University, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=case1151680415

    Chicago Manual of Style (17th edition)

case1151680415
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© 2006, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.