D7Ertd443e-KO Mouse

D7Ertd443e is an alias for FATS (fragile site-associated tumor suppressor). FATS is an (E2-independent) E3 ubiquitin-conjugating enzyme. It has been implicated in tumor-related processes, and its role in immune cells was previously unknown. It may be involved in pathways related to tumor development and immunity [1].

Fats-/-mice (gene knockout mouse model) show reduced subcutaneous B16 melanoma and H7 pancreatic tumor growth compared to wild-type controls. This reduced tumor growth is macrophage-dependent and is associated with a shift of macrophages within the tumor from tumor-promoting M2-like to antitumor M1-like macrophages. FATS deficiency promotes M1 polarization by disrupting the NF-κB/IκBα negative feedback loops, stimulating and prolonging NF-κB activation, and indirectly enhancing both CD4+ T helper type 1 (Th1) and cytotoxic T lymphocyte (CTL) adaptive immune responses to promote tumor regression. Transfer of Fats-/-macrophages protects mice against B16 melanoma [1].

In conclusion, FATS (D7Ertd443e) functions as an immune regulator. The Fats-/-mouse model reveals its significance in tumor immunity, suggesting that it is a potential target in cancer immunotherapy. Understanding its role in macrophage polarization and immune response activation can provide new strategies for cancer treatment [1].

References:

1. Zhang, Lijuan, Zhang, Kai, Zhang, Jieyou, Yao, Zhi, Zhang, Rongxin. 2021. Loss of fragile site-associated tumor suppressor promotes antitumor immunity via macrophage polarization. In Nature communications, 12, 4300. doi:10.1038/s41467-021-24610-x. https://pubmed.ncbi.nlm.nih.gov/34262035/