Pigmented uveal tumours in a transgenic mouse model.
OBJECTIVE
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.


CONCLUSIONS
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.
Kramer
T R
TR
Department of Ophthalmology, University of Arizona, Tucson 85719, USA.
Powell
M B
MB
Wilson
M M
MM
Salvatore
J
J
Grossniklaus
H E
HE
D000818:Animals; D002455:Cell Division; D004195:Disease Models, Animal; D011905:Genes, ras; D008544:Melanocytes / Q000473:pathology; D008546:Melanoma, Experimental / Q000235:genetics / Q000648:ultrastructure*; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D009154:Mutation; D010857:Pigment Epithelium of Eye / Q000473:pathology; D014604:Uveal Neoplasms / Q000235:genetics / Q000648:ultrastructure*