Suppression of progressive loss of coat color in microphthalmia-vitiligo mutant mice.
The coat color of C57BL/6-Mitfvit/vit mice whitens with age, because of a one-nucleotide mutation in the DNA-binding region of the microphthalmia-associated transcription factor (MITF), which plays an important role in melanocyte growth and differentiation. To investigate the signals regulating MITF function, we prepared transgenic mice expressing three of the external signals that are important for melanocyte development, i.e., hepatocyte growth factor (HGF), stem cell factor (SCF), and endothelin-3 (ET3), and crossed these mice with Mitfvit/vit mice. We found that the age-dependent coat color whitening of the Mitfvit/vit mice was completely suppressed by the overexpression of HGF or SCF in the skin, but not by that of ET3. Moreover, HGF, but not ET3, promoted the proliferation of Mitfvit/vit mice-derived melanocytes in culture. These results suggest that the signals from exogenous HGF and SCF rescued the mi-vitiligo mutation and also that ET3 does not stimulate the common signal transduction pathway for MITF activation shared by HGF and SCF.
Kurita
Kei
K
Biological Science Research Center, Research and Technology Headquarters, LION Corporation, Odawara, Japan. kei-k@lion.co.jp
Nishito
Maki
M
Shimogaki
Hisao
H
Takada
Koji
K
Yamazaki
Hidetoshi
H
Kunisada
Takahiro
T
D000367:Age Factors; D000818:Animals; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics*; D019334:Endothelin-3 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D006197:Hair / Q000502:physiology; D006200:Hair Color / Q000235:genetics*; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008544:Melanocytes / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D051739:Microphthalmia-Associated Transcription Factor; D009154:Mutation; D012038:Regeneration; D015398:Signal Transduction; D019089:Stem Cell Factor / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D013489:Suppression, Genetic; D014157:Transcription Factors / Q000235:genetics*; D014820:Vitiligo / Q000235:genetics*
D004268:DNA-Binding Proteins; D019334:Endothelin-3; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D019089:Stem Cell Factor; D014157:Transcription Factors; D017228:Hepatocyte Growth Factor