Tnfaip8l2-KO Mouse

Tnfaip8l2, also known as TIPE2, is a newly identified immune negative regulator belonging to the TNFAIP8 family. It plays a crucial role in maintaining immune homeostasis, with its functions associated with multiple pathways. For instance, it can interact with the RAC1-MTORC1 axis, which is involved in autophagy and mTORC1-related signaling [1,2].

In Tnfaip8l2-deficient (Tnfaip8l2-/-) mouse models, several significant phenotypes were observed. Tnfaip8l2 deficiency led to features of oxidative stress in cochlear hair cells and age-related hearing degeneration, similar to mTORC1-over-activated Tsc1-cKO mice. Rapamycin, an mTORC1 inhibitor, mitigated the hearing dysfunction caused by Tnfaip8l2-deficiency. Mechanistically, TNFAIP8L2 was found to regulate mTORC1 signaling by inhibiting the GTPase activity of RHEB and RAC1 [2]. Additionally, in an LPS-induced mouse endotoxemia model, Tnfaip8l2 deficiency exacerbated the inflammatory response and lung injury by controlling the MTOR activity [1].

In conclusion, Tnfaip8l2 is essential for maintaining immune homeostasis and normal physiological functions. Through gene knockout mouse models, its role in age-related hearing loss and endotoxemia-induced lung injury has been revealed. These findings suggest Tnfaip8l2 could be a potential therapeutic target for related diseases [1,2].