Leptin-Deficient Mice Backcrossed to the BALB/cJ Genetic Background Have Reduced Adiposity, Enhanced Fertility, Normal Body Temperature, and Severe Diabetes

Jul 19, 2001Endocrinology

Leptin-deficient mice on a BALB/cJ background have less body fat, better fertility, normal body temperature, and severe diabetes

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Abstract

BALB/cJ ob/ob mice showed a 35-40% reduction in body weight compared to C57BL/6J ob/ob mice at 27 weeks of age.

A 60% decrease in white adipose tissue mass was observed in BALB/cJ ob/ob mice.
Food intake levels were similar between the two strains, indicating different energy utilization.
BALB/cJ ob/ob mice exhibited elevated insulin and triglyceride levels, suggesting a worsening of diabetes.
Unlike C57BL/6J ob/ob mice, both male and female BALB/cJ ob/ob mice were capable of reproduction after prolonged mating periods.
At thermoneutrality, BALB/cJ ob/ob mice had a body temperature 2.9°C higher than C57BL/6J ob/ob mice.
BALB/cJ ob/ob mice showed prolonged cold tolerance when exposed to 4°C.

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A deficiency of leptin synthesis in mice results in a complex phenotype characterized by morbid obesity, diabetes, sterility, and defective thermogenesis. To determine whether the genetic background could alter the pleiotropic effects of leptin deficiency, we backcrossed the ob mutation for 10 generations from the C57BL/6J to the BALB/cJ genetic background. Compared with C57BL/6J ob/ob mice, BALB/cJ ob/ob mice showed at 27 wk of age a 35-40% reduction in body weight attributed to a 60% decrease in white adipose tissue mass. Food intake was not significantly different between the two obese strains, suggesting distinct utilization of energy intake. In the fed state, BALB/cJ ob/ob mice had elevated insulin and triglycerides levels, demonstrating a worsening effect on diabetes. At the reproductive level and in contrast to sterile C57BL/6J ob/ob mice, male and female BALB/cJ ob/ob mice were capable of reproducing after a mating period of 16 and 32 wk, respectively. At thermoneutrality, the body temperature of BALB/cJ ob/ob mice was 2.9 C higher than that of C57BL/6J ob/ob mice, whereas exposure of both groups to 4 C demonstrated a prolonged cold tolerance of BALB/cJ ob/ob mice. These studies show that the abnormalities caused by leptin deficiency can be genetically dissected and separated from each other, suggesting discrete pathways controlled by leptin modifier genes.

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Leptin-Deficient Mice Backcrossed to the BALB/cJ Genetic Background Have Reduced Adiposity, Enhanced Fertility, Normal Body Temperature, and Severe Diabetes

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