Hyperpigmentation and melanocytic hyperplasia in transgenic mice expressing the human T24 Ha-ras gene regulated by a mouse tyrosinase promoter

Mol Carcinog. 1995 Feb;12(2):82-90. doi: 10.1002/mc.2940120205.


The tyrosinase promoter has been used to target expression of the mutated human T24 Ha-ras oncogene in pigment-producing cells of transgenic mice. Two independent founder mice carrying the transgene survived and showed the same distinct phenotype of mutated coat color, deeply pigmented skin with multiple nevi, and twirling behavior. The offspring of one of these founders were developed into a line that stably expressed the same phenotype. Histopathological analysis of the tissues revealed hyperpigmentation and/or melanocytic hyperplasia in the skin, eyes, inner ear, and meningeal membranes in the brain. Reverse transcriptase-polymerase chain reaction analysis revealed expression of the transgene in skin, brain, and spleen. We propose that these transgenic mice will be a model for studying the process of multistage melanoma carcinogenesis and a system for evaluating potential chemopreventive agents.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • DNA Primers / chemistry
  • Genes, ras*
  • Humans
  • Hyperplasia
  • Melanocytes / pathology*
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Monophenol Monooxygenase / genetics
  • Pigmentation
  • Precancerous Conditions / pathology
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Rats
  • Transfection


  • DNA Primers
  • Monophenol Monooxygenase
  • HRAS protein, human
  • Proto-Oncogene Proteins p21(ras)