Switching of Melanocyte Pigmentation Associated with Pituitary Pars Intermedia Tumors in Rb+/- and p27-/- Female Mice with Yellow Pelage
Abstract:As an incidental finding in a study of mammary tumorigenesis, two lines of genetically engineered mice were observed to develop pigmentation changes of the fur. Mice with targeted mutations of the Rb1 (Rb) and Cdkn1b (p27kip1) genes were crossed from C57BL/6 (black coat color; eumelanin) and 129Sv (wild-type agouti coat color) backgrounds, respectively, to one with a dominant yellow coat color (phaeomelanin) carrying a transgene for Agouti under a keratinocyte specific promoter. Both Rb+/- and p27-/- mice developed pituitary tumors of the pars intermedia that were associated with a switch to black (eumelanic) fur but were not observed in sibling Rb+/+ and p27+/+ mice. This phenomenon was observed first in the vibrissae and, subsequently one to two weeks later, as periorbital and dorsal patches, and was associated with pituitary lesions larger than four millimeters in the longest dimension. In Rb+/- mice, pigmentation change preceded a moribund state attributable to the tumors by two to four weeks, whereas in p27-/- mice, the pigmentation alteration was earlier, more gradual, and prolonged. The switch from phaeomelanin to eumelanin in the fur is most likely due to out-competition of the agouti gene product by α-melanocyte-stimulating hormone from the pituitary tumors, an effect masked in black or agouti mice.
Document Type: Research Article
Affiliations: 1: The Scripps Research Institute, Department of Molecular Biology, MB-7, 10550 North Torrey Pines Road, La Jolla, California 92037 2: Department of Histopathology, Rotherham General Hospital, Rotherham, S60 2UD, United Kingdom 3: GlaxoSmithKline, Research Triangle Park, North Carolina 27709 4: Piedmont Research Center, 3300 Gateway Centre, Morrisville, North Carolina 27560
Publication date: February 1, 2003
Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.
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