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Requirement for leptin receptor in mammary epithelium for alveolar development



Requirement for leptin receptor in mammary epithelium for alveolar development



FASEB Journal 18(4-5): Abst 451 1



Mice lacking leptin or leptin receptor have impaired mammary development. Whether this is due to local leptin requirements within the mammary gland or to alterations in systemic physiology is unclear. To determine if leptin directly impacts mammary development, mammary epithelium was transplanted from wild-type (Lepr+/+) or leptin receptor deficient (Lepr-/-) donors into gland-free mammary fat pads of C57BL/6J mice. Mice were mated, euthanized at various stages of pregnancy and mammary whole mount development scored on a scale of 1-5. Development of the non-pregnant mammary gland was not different between Lepr+/+ and Lepr-/- (development score of 2.1 for Lepr+/+ vs 1.8 for Lepr-/- on day 0 of pregnancy). Subsequent duct development did not appear to be impaired in Lepr-/- mammary glands. However, alveolar development was dramatically inhibited. By day 15 of pregnancy, Lepr+/+ epithelium had extensive alveolar development, which was greatly reduced in glands containing epithelium from Lepr-/- donors (development score of 5.1 for Lep+/+ vs 3.9 for Lep-/-). Since the only tissue lacking leptin receptor was the mammary epithelium, this suggests that failure of mammary development in Lep-/- and Lepr-/- mice is due at least in part to a leptin requirement by the mammary epithelial cells, specifically a requirement for leptin in alveolar development.

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