Br J Ophthalmol 1998;82:953-960 ( August )

Pigmented uveal tumours in a transgenic mouse model

Theresa R Kramer,^a Marianne B Powell,^b Matthew M Wilson,^c Jennifer Salvatore,^b Hans E Grossniklaus^c

^a Departments of Ophthalmology and Pathology, University of Arizona, Tucson, Arizona, USA, ^b Arizona Cancer Center, University of Arizona Health Sciences Center, Tucson, Arizona, USA, ^c Department of Ophthalmology, Emory Eye University, Atlanta, Georgia, USA

Correspondence to: Theresa R Kramer, MD, Departments of Ophthalmology and Pathology, University of Arizona, 1801 N Campbell Avenue Tucson, AZ 85719, USA.

Accepted for publication 29 January 1998

AIMS/BACKGROUNDThe 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.
METHODSTransgenic 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.
RESULTSSix 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.
CONCLUSIONPigmented 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.

Keywords: histopathology; melanoma model; transgenic mice; uveal melanoma

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© 1998 by British Journal of Ophthalmology
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