Development of a new mouse model (xeroderma pigmentosum a-deficient, stem cell factor-transgenic) of ultraviolet B-induced melanoma.
It is well established that exposure to sunlight or ultraviolet radiation (UVR) is the major environmental risk factor for the development of skin neoplasms. To date, however, there have been few appropriate mouse models available for studying the role of UVR in melanoma carcinogenesis, mainly because of the murine lack of the epidermal melanocyte, which is a major source of origin of human melanoma. In this study, we established xeroderma pigmentosum group A gene-deficient, stem cell factor-transgenic mice, which are defective in the repair of damaged DNA and do have epidermal melanocytes. The mice were exposed to UVR three times a week for 10 wk. More than 30% of the irradiated mice developed tumors of melanocyte origin that metastasized to the lymph nodes. Histologically, proliferated cells exhibited lentigo maligna melanoma or nodular melanoma. Immunohistochemistry confirmed that the tumor cells were characteristic of melanoma. Non-irradiated mice did not develop skin tumors spontaneously. The newly generated model mouse might be useful for studying the photobiological aspects of human melanoma, because the mice developed melanoma from epidermal melanocytes only after UVR exposures.
Yamazaki
Fumikazu
F
Department of Dermatology, Kansai Medical University, Moriguchi, Osaka, Japan. yamazakf@takii.kmu.ac.jp
Okamoto
Hiroyuki
H
Matsumura
Yasuhiro
Y
Tanaka
Kiyoji
K
Kunisada
Takahiro
T
Horio
Takeshi
T
D000818:Animals; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics; D004195:Disease Models, Animal; D008546:Melanoma, Experimental / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012867:Skin / Q000473:pathology / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D019089:Stem Cell Factor / Q000235:genetics*; D019076:Transgenes; D014466:Ultraviolet Rays; D051760:Xeroderma Pigmentosum Group A Protein
D004268:DNA-Binding Proteins; D019089:Stem Cell Factor; D051760:Xeroderma Pigmentosum Group A Protein; C497315:Xpa protein, mouse