A novel hairless mouse model for malignant melanoma

Nguyen Dinh Thang, Ichiro Yajima, Kaoru Nakagawa, Toyonori Tsuzuki, Mayuko Y. Kumasaka, Nobutaka Ohgami, Thuy B. Ly, Takashi Iwamoto, Daisuke Watanabe, Masashi Kato

Research output: Contribution to journalArticle

9 Citations (Scopus)

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. 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.

Original languageEnglish
Pages (from-to)207-212
Number of pages6
JournalJournal of Dermatological Science
Volume65
Issue number3
DOIs
Publication statusPublished - 2012 Mar 1
Externally publishedYes

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Tumors
Animals
Biomarkers
Binders
Skin
Phosphotransferases
Cells
Molecules

Keywords

  • Animal model
  • Hairlessness
  • Melanoma
  • MOBKL2B

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology

Cite this

Thang, N. D., Yajima, I., Nakagawa, K., Tsuzuki, T., Kumasaka, M. Y., Ohgami, N., ... Kato, M. (2012). A novel hairless mouse model for malignant melanoma. Journal of Dermatological Science, 65(3), 207-212. https://doi.org/10.1016/j.jdermsci.2011.10.010

A novel hairless mouse model for malignant melanoma. / Thang, Nguyen Dinh; Yajima, Ichiro; Nakagawa, Kaoru; Tsuzuki, Toyonori; Kumasaka, Mayuko Y.; Ohgami, Nobutaka; Ly, Thuy B.; Iwamoto, Takashi; Watanabe, Daisuke; Kato, Masashi.

In: Journal of Dermatological Science, Vol. 65, No. 3, 01.03.2012, p. 207-212.

Research output: Contribution to journalArticle

Thang, ND, Yajima, I, Nakagawa, K, Tsuzuki, T, Kumasaka, MY, Ohgami, N, Ly, TB, Iwamoto, T, Watanabe, D & Kato, M 2012, 'A novel hairless mouse model for malignant melanoma', Journal of Dermatological Science, vol. 65, no. 3, pp. 207-212. https://doi.org/10.1016/j.jdermsci.2011.10.010
Thang, Nguyen Dinh ; Yajima, Ichiro ; Nakagawa, Kaoru ; Tsuzuki, Toyonori ; Kumasaka, Mayuko Y. ; Ohgami, Nobutaka ; Ly, Thuy B. ; Iwamoto, Takashi ; Watanabe, Daisuke ; Kato, Masashi. / A novel hairless mouse model for malignant melanoma. In: Journal of Dermatological Science. 2012 ; Vol. 65, No. 3. pp. 207-212.
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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. 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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AU - Ohgami, Nobutaka

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N2 - 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.

AB - 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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