Switching of melanocyte pigmentation associated with pituitary pars intermedia tumors in Rb+/- and p27-/- female mice with yellow pelage.
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 alpha-melanocyte-stimulating hormone from the pituitary tumors, an effect masked in black or agouti mice.
Smith
Adrian P L
AP
The Scripps Research Institute, Department ofMolecular Biology, MB-7, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Henze
Martha
M
Osborn
Kent G
KG
Lee
John A
JA
Bortner
Donna M
DM
Rosenberg
Michael P
MP
Reed
Steven I
SI
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005260:Female; D006200:Hair Color; D008297:Male; D008544:Melanocytes / Q000473:pathology*; D051379:Mice; D010375:Pedigree; D010858:Pigmentation; D010911:Pituitary Neoplasms / Q000235:genetics / Q000473:pathology*; D016160:Retinoblastoma Protein / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D016160:Retinoblastoma Protein; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27