Table 4.
Genetically engineered mouse models of uveal melanoma
Model genotype | Induction | Phenotype | Original Publication (Laboratory of origin) |
---|---|---|---|
Dct‐rtTA/+; tet‐HA‐GNAQ Q209L/+; p16p19KO | 5‐ to 6‐week‐old mice; doxycycline in food | >50% of mice developed cutaneous melanoma; no report of lesions in the uveal tract | Feng et al. (2014) (J. Silvio Gutkind) |
Rosa26‐floxed stop‐GNAQ Q209L/+; Mitf‐cre/+ | Embryonic (E15.5) activation by constitutive Cre driver | Skin hyperpigmentation overt uveal melanoma and occasional dermal melanoma at 3 months in 15/15 mice; melanocytic neoplasia of the leptomeninges, harderian gland, cochlea, and vestibular system; putative metastases in the lungs at 3 months in 18/19 mice | Huang et al. (2015) (Catherine Van Raamsdonk) |
Rosa26‐floxed stop‐GNAQ Q209L/+; Tyrosinase‐creER/+ | 8‐week‐old mice; daily IP injection of tamoxifen and tail dip in 4‐HT for 5 days | Skin hyperpigmentation; melanocytic hyperplasia of the uveal tract (but not overt melanoma) in 3/3 mice | |
R26‐LSL‐GNA11 Q209L/+; Tyrosinase‐creERT2/+ | 4‐week‐old mice; single IP injection of tamoxifen | Skin hyperpigmentation; overt uveal and dermal melanoma at 6 months in 50% of mice; melanocytic neoplasia of the leptomeninges, third ventricle, harderian gland, and heart; putative metastases in axillary lymph nodes and lungs at 3‐6 months in 100% of mice | Moore et al. (2018) (Yu Chen) |
R26‐LSL‐GNA11 Q209L/+; BAP1lox/lox; Tyrosinase‐creERT2/+ | Compared to above: increased dermal melanoma burden and proliferative index, no change in number or size of uveal melanoma tumors or lung lesions | ||
AAV5‐CMV‐Cre or AAV5‐Trp2‐GFPCre; Lats1f/f; Lats2f/f | 2‐ to 4‐month‐old mice; suprachoroidal injection of AAV | Eye bulging at 2 months and uveal melanoma formation at 6 months in 12/14 and 8/10 mice, respectively | Li et al. (2019) (Junhao Mao) |
AAV5‐Trp2‐GFPCre; Lats1f/f; Lats2f/f; LSL‐KrasG12D | Compared to above: larger uveal melanoma tumors in 7/7 mice and reduced survival (<4 months) |