THE MURINE MISTY MUTATION - PHENOTYPIC EFFECTS ON MELANOCYTES, PLATELETS AND BROWN FAT

Although the recessive murine mutation misty (m) is well known, its ph enotype pe has never been reported beyond brief descriptions of a dilu tion of coat Color and white spotting of the belly and extremities, su ggesting a developmental mutation. A report in abstract has also sugge sted effects on white fat and body weight. Here, we report effects of the homozygous misty mutation on an unusual combination of three cell types: melanocytes, platelets, and brown fat. Brown fat appeared to be completely absent fr-om all expected locations in neonatal m/m mice. A prolonged bleeding time was observed; platelet count and platelet se rotonin and ATP levels were normal, but the level of ADP in m/m platel ets was low Primary cultures and immortal lines of melanocytes from m/ m mice showed several abnormalities. There was a marked deficiency in net proliferation, suggesting that the color dilution and spotting in vivo may result from reduced numbers of melanocytes and their precurso rs. m/m melanocytes were also hyperdendritic in morphology, over-produ ced melanin, and had deficient responses to the cAMP agonists cholera toxin and melanocyte-stimulating hormone, which normally promote melan in production. The misty gene product map be involved in adenine nucle otide metabolism or signaling.