International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


POSTER 163 - GENETIC DISSECTION OF DIET-INDUCED OBESITY RESISTANCE IN B6.A CHROMOSOME SUBSTITUTION STRAINS

Burrage L
Case Western Reserve University

Co-Authors: 1) Hill A, 2) Singer J, 1) Olszens K, 3) Conti D, 1) Witte J, 2) Lander E, 1) Nadeau J
Institutions: 1) Case Western Reserve University, 2) Whitehead Institute/Massachusetts Institute of Technology, 3) University of Southern California

The new panel of B6.A chromosome substitution strains provides a powerful tool for dissecting complex genetic traits. Because the C57BL/6J and A/J inbred strains differ in their susceptibility to obesity on a high fat, high sucrose diet, we used the B6.A panel to identify the chromosomal location of genes associated with resistance to diet-induced obesity. We placed 20 males from each strain on a high fat, high sucrose diet at 35 days of age and collected body weights every two weeks for approximately 100 days. We found that A/J-derived chromosomes 3, 4, 6, 7, 8, 10, 11, 12, 13, 14, 15, 16, 17, 18, and Y conferred resistance to diet-induced obesity, whereas chromosomes 1, 2, 9, 19, and X did not confer resistance. Preliminary studies of F2 intercross progeny derived from B6.A1, B6.A2, B6.A9, B6.A19, and B6.AX suggest that these chromosomes harbor QTLs that have opposing effects on obesity resistance. Overall, by analyzing a total of 400 mice, we detected at least 15 and perhaps as many as 20 genes associated with diet-induced obesity resistance. We are currently pursuing a novel whole genome scan approach with F2 intercross progeny derived from each substitution strain to identify QTLs and ultimately genes controlling resistance to diet-induced obesity. With the sequencing of these two inbred strains nearly complete and the availability of BAC libraries that can be utilized for transgenic studies in genetically-engineered mice, the B6.A chromosome substitution strains are emerging as powerful tools for studying complex genetic traits, such as obesity.


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