Aberrant melanogenesis and melanocytic tumour development in transgenic mice that carry a metallothionein/ret fusion gene

Takashi Iwamoto, Masahide Takahashi, Masafumi Ito, Kiyohiro Hamatani, Masaharu Ohbayashi, Worawidh Wajjwalku, Ken Ichi Isobe, Izumi Nakashima

Research output: Contribution to journalArticlepeer-review

117 Citations (Scopus)

Abstract

We generated four independent transgenic mouse lines that showed severe melanosis of the whole body by introducing the ret oncogene fused to the mouse metallothionein (MT)-I promoter -enhancer (MT/ret). Whereas melanogenesis was accelerated without distinct proliferative disorders in one line, melanocytic tumours frequently developed in the other three lines. Northern hybridization and in situ hybridization analyses showed that tumour cells and non-tumorous melanin-producing cells expressed the transgene at high levels. The aberrant melanogenesis and tumour development were influenced by genetic and environmental factors. Furthermore, crossbreeding experiments between the transgenic mice and Wv mice suggested that the ret gene product can partially compensate for the defect of melanocyte development in Wv mice. This is a novel mammalian model in which melanosis and melanocytic tumours develop stepwise, triggered by a single transgene.

Original languageEnglish
Pages (from-to)3167-3175
Number of pages9
JournalEMBO Journal
Volume10
Issue number11
Publication statusPublished - 1991
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Neuroscience
  • Molecular Biology
  • General Biochemistry,Genetics and Molecular Biology
  • General Immunology and Microbiology

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