PIGMENTED UVEAL TUMORS IN A TRANSGENIC MOUSE MODEL

Aims/background-The authors have developed transgenic mouse strains at the Arizona Cancer Center using a tyrosinase promoter to target expre ssion of the mutated T24 Ha-ras gene in melanin producing cells. Histo pathology and electron microscopy (EM) were performed to characterise the intraocular tumours observed phenotypically. Methods-Transgenic TP ras mice (n=8) and normal, age matched control mice (n=6) were sacrifi ced at 3 weeks, 6 weeks, 7 weeks, 4 months, 5 months, 9 months, and 11 months. Six were processed in formalin for light microscopic examinat ion and eight in a glutaraldehyde/formalin solution for electron micro scopic examination. Results-Six of the TPras mice were found to have b ilateral 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 intracyto plasmic melanin. By EM two populations of cells were identified, inclu ding spindle-shaped cells with round to oval melanin granules and cubo idal 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. Cy tological features included increased N:C ratios, nuclear pleomorphism , and prominent nucleoli. The uveal tract was normal in both eyes in a ll of the control animals. Conclusion-Pigmented intraocular tumours de veloped in transgenic strains of mice that express a mutated Ha-ras ge ne in melanin producing cells. The morphology was most consistent with a melanoma in two of the mice and a benign melanocytic/RPE proliferat ion in the remaining mice.