Revealing mitf functions and visualizing allografted tumor metastasis in colorless and immunodeficient Xenopus tropicalis.

Transparent immunodeficient animal models not only enhance in vivo imaging investigations of visceral organ development but also facilitate in vivo tracking of transplanted tumor cells. However, at present, transparent and immunodeficient animal models are confined to zebrafish, presenting substantial challenges for real-time, in vivo imaging studies addressing specific biological inquiries. Here, we employed a mitf-/-/prkdc-/-/il2rg-/- triple-knockout strategy to establish a colorless and immunodeficient amphibian model of Xenopus tropicalis. By disrupting the mitf gene, we observed the loss of melanophores, xanthophores, and granular glands in Xenopus tropicalis. Through the endogenous mitf promoter to drive BRAFV600E expression, we confirmed mitf expression in melanophores, xanthophores and granular glands. Moreover, the reconstruction of the disrupted site effectively reinstated melanophores, xanthophores, and granular glands, further highlighting the crucial role of mitf as a regulator in their development. By crossing mitf-/- frogs with prkdc-/-/il2rg-/- frogs, we generated a mitf-/-/prkdc-/-/il2rg-/- Xenopus tropicalis line, providing a colorless and immunodeficient amphibian model. Utilizing this model, we successfully observed intravital metastases of allotransplanted xanthophoromas and migrations of allotransplanted melanomas. Overall, colorless and immunodeficient Xenopus tropicalis holds great promise as a valuable platform for tumorous and developmental biology research.

Disruption of tp53 leads to cutaneous nevus and melanoma formation in Xenopus tropicalis.

In humans, germline TP53 mutations predispose carriers to a wide spectrum of cancers, which is known as Li-Fraumeni syndrome (LFS). To date, the association of melanomas with LFS remains unestablished. No melanomas have been reported in any P53-modified mouse models either. In this study, we show that targeted disruption of P53 at the DNA-binding domain in Xenopus tropicalis recapitulates LFS, with the formation of soft-tissue sarcomas and pancreatic ductal adenocarcinoma. Interestingly, 19% of the 14-month-old tp53Δ7/Δ7 homozygotes and 18% of tp53+/Δ7 heterozygotes spontaneously developed small nevi and non-invasive melanomas. Large invasive melanomas were also observed in other older homozygous mutants, with about 7.9% penetrance. Our data suggest that more dermatologic investigation of LFS patients should be able to settle the association of melanoma with LFS in epidemiology. Our model is also valuable for further investigation of the molecular mechanism underlying melanoma progression upon germline alteration of the tp53 locus.