Spontaneous uveal amelanotic melanoma in transgenic Tyr-RAS Ink4a/Arf-/- mice

William H. Tolleson, Jason C. Doss, John Latendresse, Alan R. Warbritton, William B. Melchior, Lynda Chin, Richard R. Dubielzig, Daniel Albert

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Objective: To characterize a murine model of spontaneous amelanotic melanoma arising in the uvea of transgenic mice bearing a targeted deletion of the Ink4a/Arf tumor suppressor locus (exons 2 and 3) and expressing human H-ras controlled by the human tyrosinase promoter. Methods: Ocular lesions developed in 20 (15.7%) of 127 male albino Tyr-RAS+ Ink4a/Arf-/- transgenic FVB/N mice within 6 months, and were evaluated histologically and ultrastructurally. Results: Uveal melanomas were locally invasive but confined to the eye, with no evidence of metastasis. Tumor cells exhibited epithelioid and spindle-shaped morphological features and closely resembled the human counterpart. Melan-A, S100 and neuron-specific enolase expression were detected immunohistochemically. Melanosomal structures were detected using electron microscopy. The retinal pigment epithelium was intact above small melanomas, and electron microscopy of the tumors failed to show the presence of basement membrane formation or desmosomes. Conclusion: Spontaneous uveal malignant melanomas occurring in male Tyr-RAS+ Ink4a/Arf-/- transgenic mice arise within the choroid or ciliary body and share histopathological features characteristic of human uveal melanoma. Clinical Relevance: Uveal melanoma research has benefited from xenograft models, but engineered mouse models of spontaneous uveal amelanotic melanoma will undoubtedly further our understanding of the genetic underpinning for this disease.

Original languageEnglish (US)
Pages (from-to)1088-1094
Number of pages7
JournalArchives of ophthalmology
Volume123
Issue number8
DOIs
StatePublished - Aug 1 2005
Externally publishedYes

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Amelanotic Melanoma
Transgenic Mice
Melanoma
Electron Microscopy
Uvea
MART-1 Antigen
Epithelioid Cells
Neoplasms
Desmosomes
Ciliary Body
Inborn Genetic Diseases
Choroid
Monophenol Monooxygenase
Phosphopyruvate Hydratase
Retinal Pigment Epithelium
Basement Membrane
Heterografts
Exons
Uveal melanoma
Neoplasm Metastasis

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Tolleson, W. H., Doss, J. C., Latendresse, J., Warbritton, A. R., Melchior, W. B., Chin, L., ... Albert, D. (2005). Spontaneous uveal amelanotic melanoma in transgenic Tyr-RAS Ink4a/Arf-/- mice. Archives of ophthalmology, 123(8), 1088-1094. https://doi.org/10.1001/archopht.123.8.1088

Spontaneous uveal amelanotic melanoma in transgenic Tyr-RAS Ink4a/Arf-/- mice. / Tolleson, William H.; Doss, Jason C.; Latendresse, John; Warbritton, Alan R.; Melchior, William B.; Chin, Lynda; Dubielzig, Richard R.; Albert, Daniel.

In: Archives of ophthalmology, Vol. 123, No. 8, 01.08.2005, p. 1088-1094.

Research output: Contribution to journalArticle

Tolleson, WH, Doss, JC, Latendresse, J, Warbritton, AR, Melchior, WB, Chin, L, Dubielzig, RR & Albert, D 2005, 'Spontaneous uveal amelanotic melanoma in transgenic Tyr-RAS Ink4a/Arf-/- mice', Archives of ophthalmology, vol. 123, no. 8, pp. 1088-1094. https://doi.org/10.1001/archopht.123.8.1088
Tolleson WH, Doss JC, Latendresse J, Warbritton AR, Melchior WB, Chin L et al. Spontaneous uveal amelanotic melanoma in transgenic Tyr-RAS Ink4a/Arf-/- mice. Archives of ophthalmology. 2005 Aug 1;123(8):1088-1094. https://doi.org/10.1001/archopht.123.8.1088
Tolleson, William H. ; Doss, Jason C. ; Latendresse, John ; Warbritton, Alan R. ; Melchior, William B. ; Chin, Lynda ; Dubielzig, Richard R. ; Albert, Daniel. / Spontaneous uveal amelanotic melanoma in transgenic Tyr-RAS Ink4a/Arf-/- mice. In: Archives of ophthalmology. 2005 ; Vol. 123, No. 8. pp. 1088-1094.
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