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Diabetes 53:245-249, 2004
© 2004 by the American Diabetes Association, Inc.


Brief Genetics Report

Identification of Major Quantitative Trait Loci Controlling Body Weight Variation in ob/ob Mice

Jonathan P. Stoehr1, Jessica E. Byers2, Susanne M. Clee1, Hong Lan1, Igor V. Boronenkov1, Kathryn L. Schueler1, Brian S. Yandell3, and Alan D. Attie1

1 Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin
2 Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, Wisconsin
3 Departments of Statistics and Horticulture, University of Wisconsin-Madison, Madison, Wisconsin

The adipocyte hormone leptin constitutes an important component of the regulation of energy homeostasis; leptin-deficient animals, such as obese mice, are strikingly overweight. The seemingly uninhibited weight gain in obese mice belies the fact that control of energy homeostasis remains under precise, heritably modifiable control. Herein, we report large, heritable differences in body weight and food intake between BTBR-ob/ob and B6-ob/ob mice. We have identified two loci, called modifier of obese (Moo1 and Moo2), that explain the majority of the heritable variance in (BTBR x B6) F2-ob/ob mice. Using interval-specific congenic mouse lines, we mapped Moo1 to an 8-Mb segment of chromosome 2 and demonstrated that Moo1 exerts its effects primarily by regulating total fat mass. Although null alleles of leptin are rare, the majority of overweight adults are leptin resistant, suggesting that leptin-independent pathways, such as those studied here, are important regulators of energy homeostasis. Thus, the identification of these loci may provide important new insights into the pathogenesis of human obesity.


Address correspondence and reprint requests to Alan D. Attie., Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Dr., Madison, WI 53706. E-mail: attie{at}biochem.wisc.edu


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Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2004 by the American Diabetes Association.