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    Br J Ophthalmol. 1998 Aug;82(8):953-60.

    Pigmented uveal tumours in a transgenic mouse model.

    Kramer TR, Powell MB, Wilson MM, Salvatore J, Grossniklaus HE.

    Department of Ophthalmology, University of Arizona, Tucson 85719, USA.

    AIMS/BACKGROUND: The authors have developed transgenic mouse strains at the Arizona Cancer Center using a tyrosinase promoter to target expression of the mutated T24 Ha-ras gene in melanin producing cells. Histopathology and electron microscopy (EM) were performed to characterise the intraocular tumours observed phenotypically. METHODS: Transgenic TPras mice (n = 8) and normal, age matched control mice (n = 6) were sacrificed at 3 weeks, 6 weeks, 7 weeks, 4 months, 5 months, 9 months, and 11 months. Six were processed in formalin for light microscopic examination and eight in a glutaraldehyde/formalin solution for electron microscopic examination. RESULTS: Six of the TPras mice were found to have bilateral pigmented melanocytic/RPE proliferations of the uveal tract. The cytological characteristics of the tumours included low nuclear to cytoplasmic ratios (N:C ratios), bland nuclei, and abundant intracytoplasmic melanin. By EM two populations of cells were identified, including spindle-shaped cells with round to oval melanin granules and cuboidal cells with apically located, cigar-shaped, melanin granules, and basement membrane formation. A 3 week and an 11 month old TPras mouse had a higher grade, bilateral, melanocytic proliferation of the uveal tract which, although not metastatic, was morphologically melanoma. Cytological features included increased N:C ratios, nuclear pleomorphism, and prominent nucleoli. The uveal tract was normal in both eyes in all of the control animals. CONCLUSION: Pigmented intraocular tumours developed in transgenic strains of mice that express a mutated Ha-ras gene in melanin producing cells. The morphology was most consistent with a melanoma in two of the mice and a benign melanocytic/RPE proliferation in the remaining mice.

    PMID: 9828784 [PubMed - indexed for MEDLINE]

    PMCID: 1722710

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