Tg(Grm1) transgenic mice: A murine model that mimics spontaneous uveal melanoma in humans?

•Tg(Grm1) mice are a promising new animal model for spontaneous uveal melanoma.•Numerous proliferative (Ki-67 positive) cells are located in the markedly thickened choroid of Tg(Grm1) mice.•Choroidal cells of Tg(Grm1) animals are positive for tumor markers like MelanA and S100B.•In humans, the expression of GRMs is significantly increased in uveal tumor tissue.

Although rare, uveal melanoma (UM) is the most common primary intraocular tumor in adults. About half of UM patients develop metastatic disease typically in the liver and die within a short period, due to ineffective systemic therapies. UM has unique and distinct genetic features predictive of metastasis. Animal models are required to improve our understanding of therapeutic options in disseminated UM. Since spontaneous murine UM models are lacking, our aim was to analyze the suitability of the established transgenic melanoma mouse model Tg(Grm1) as a new UM model system. We demonstrated that adult Grm1 transgenic mice develop choroidal thickening and uveal melanocytic neoplasia with expression of the melanocytic markers S100B and MelanA. Further, we showed that GRM1 is expressed in human UM, similar to skin melanoma. This study presents a new mouse model for spontaneous UM and suggests that the glutamate signaling pathway is a possible target for UM therapy.