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. Conclusion: 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.
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