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

摘要

Hybrid transgenic/genetically obese mice were bred to evaluate the effects of obesity on mammary tumor development (MT). In the TGF-alpha/Lep(sup ob) Incidence Study, Lep(+)Lep(+) lean, Lep(+)Lep(sup ob) lean, and Lep(sup ob) Lep(sup 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-alpha/ Lep(+)Lep(sup ob) mice were food restricted at 50% of ad libitum for 3 wk periods followed by 3 wk of ad libitum feeding resulting in (caret).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-a/Lep(+)Lep(+) 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-alpha/Lepr(sup db) has also been established. The Lepr(sup db) Incidence Study has completed enrollment. As with the Lep(sup ob) mice, obese mice are dying at young ages, and the TGF-alpha/Lepr(+)Lepr(sup db) lean mice weigh more than Lepr(+)Lepr(+) 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.