title: A novel hairless mouse model for malignant melanoma.
abstract: BACKGROUND
  An appropriate animal model for malignant melanoma could be a strong tool to develop biomarkers through analysis of melanomagenesis.
  
  
  OBJECTIVE
  Development of a novel animal model that spontaneously develops malignant melanoma with a high percentage.
  
  
  METHODS
  We crossed oncogenic RET (RFP-RET)-carrying transgenic mice of line 304/B6 (RET-mice) with hairless mice (hr/hr) and newly established hairless RFP-RET-transgenic mice of line 304-hr/hr (HL-RET-mice).
  
  
  RESULTS
  The HL-RET-mice developed hyperpigmented skin and benign melanocytic tumors without exception. More importantly, 63.8% (46/72) of the benign tumors were transformed to malignant melanoma in the HL-RET-mice. Mean time until the development of benign melanocytic tumors (2.4 months; n = 102) in the HL-RET-mice was about half of that in the original RET-mice (4.6 months; n = 20). Mean life span in the HL-RET-mice (9.7 months; n = 38) was also significantly (p < 0.01) shorter than that in the original RET-mice (10.8 months; n = 20). Since early development of tumors could contribute to shortening of the research period, HL-RET-mice could be a useful model for analysis of melanomagenesis. We then found that the expression level of Mps one binder kinase activator-like-2B (Mobkl2b) in benign tumors was higher than that in malignant melanoma in HL-RET-mice. Expression level of MOBKL2B in malignant melanoma cell lines was also lower than that in non-malignant melanocytic cells in mice and humans, suggesting that MOBKL2B could be a novel marker for malignant melanoma.
  
  
  CONCLUSIONS
  We established a novel hairless RET-transgenic mouse line spontaneously developing cutaneous malignant melanomas from benign melanocytic tumors. This mouse model may be useful to find new candidates of melanoma-related molecule.
authors.affiliation: Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, 1200 Matsumoto-cho, Kasugai-shi, Aichi, Japan.
authors.forename: Nguyen Dinh
authors.initials: ND
authors.lastname: Thang
authors.forename: Ichiro
authors.initials: I
authors.lastname: Yajima
authors.forename: Kaoru
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Toyonori
authors.initials: T
authors.lastname: Tsuzuki
authors.forename: Mayuko Y
authors.initials: MY
authors.lastname: Kumasaka
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Ohgami
authors.forename: Thuy B
authors.initials: TB
authors.lastname: Ly
authors.forename: Takashi
authors.initials: T
authors.lastname: Iwamoto
authors.forename: Daisuke
authors.initials: D
authors.lastname: Watanabe
authors.forename: Masashi
authors.initials: M
authors.lastname: Kato
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D004195:Disease Models, Animal; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008812:Mice, Hairless; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000378:metabolism; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C573237:MOBKL2B protein, mouse; D009363:Neoplasm Proteins; D051096:Proto-Oncogene Proteins c-ret; C494999:Ret protein, mouse