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Development of a New Mouse to Study the Interactions of Obesity on the Development of Breast Cancer

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Final rept. 1 Sep 1997-31 Aug 2000

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Hybrid transgenicgenetically obese mice were bred to evaluate the effects of obesity on mammary tumor development MT. In the TGF-alphaLepsup ob Incidence Study, LepLep lean, LepLepsup ob lean, and Lepsup obLepsup ob obese mice were followed. Obese mice weighed more than lean mice, but died prior to MT development. Heterozygous mice weighed more than homozygous lean mice, died younger, and had higher MT incidence. Within genotypes, mice with MT were heavier and had higher fat pad weights. WEIGHT-CYCLED TGF-alphaLepLepsup ob mice were food restricted at 50 of ad libitum for 3 wk periods followed by 3 wk of ad libitum feeding resulting in 25 reduction in caloric intake. WEIGHT-CYCLED mice had decreased incidence and increased latency of MT compared to AD LIBITUM and PAIR-FED mice. TGF-aLepLep mice fed a high-fat diet were assigned to OBESITY-PRONE and OBESITY-RESISTANT groups. OBESITY-PRONE mice developed MT at a significantly earlier age than OBESITY-RESISTANT mice and CHOW mice. A second hybrid strain, TGF-alphaLeprsup db has also been established. The Leprsup db Incidence Study has completed enrollment. As with the Lepsup ob mice, obese mice are dying at young ages, and the TGF-alphaLeprLeprsup db lean mice weigh more than LeprLepr lean mice. MT have been detected in both lean groups. All mice have been enrolled in the Lepr Diet-Induced Obesity protocol, and we have almost completed enrollment in the Weight-Cycled protocol.

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  • Medicine and Medical Research

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