Leptin-Deficient Mice Backcrossed to the BALB/cJ Genetic Background Have Reduced Adiposity, Enhanced Fertility, Normal Body Temperature, and Severe Diabetes
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 gener...
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Published in | Endocrinology (Philadelphia) Vol. 142; no. 8; pp. 3421 - 3425 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Endocrine Society
01.08.2001
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Online Access | Get full text |
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Summary: | 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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ISSN: | 0013-7227 1945-7170 |
DOI: | 10.1210/endo.142.8.8323 |