The murine misty mutation: phenotypic effects on melanocytes, platelets and brown fat

Genetics. 1998 Jan;148(1):381-90. doi: 10.1093/genetics/148.1.381.

Abstract

Although the recessive murine mutation misty (m) is well known, its phenotype has never been reported beyond brief descriptions of a dilution of coat color and white spotting of the belly and extremities, suggesting a developmental mutation. A report in abstract has also suggested 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 from all expected locations in neonatal m/m mice. A prolonged bleeding time was observed; platelet count and platelet serotonin and ATP levels were normal, but the level of ADP in m/m platelets 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 precursors. m/m melanocytes were also hyperdendritic in morphology, overproduced melanin, and had deficient responses to the cAMP agonists cholera toxin and melanocyte-stimulating hormone, which normally promote melanin production. The misty gene product may be involved in adenine nucleotide metabolism or signaling.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Adipose Tissue, Brown / abnormalities*
  • Animals
  • Bleeding Time
  • Blood Platelets / metabolism
  • Cell Division / drug effects
  • Cell Division / genetics
  • Genes / genetics*
  • Hair Color / genetics*
  • Melanocytes / cytology*
  • Melanocytes / drug effects
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mutation
  • Phenotype
  • Phenylthiourea / pharmacology
  • Pigmentation / genetics

Substances

  • Phenylthiourea
  • Adenosine Triphosphate