Otulin-flox Mouse

Otulin, also known as OTU deubiquitinase with linear linkage specificity, is a crucial deubiquitinating enzyme. It specifically hydrolyzes linear ubiquitin chains generated by the linear ubiquitin chain assembly complex (LUBAC), regulating inflammation and cell death. It is involved in pathways such as NF-κB signaling and is of great biological importance in maintaining immune homeostasis [1,2,3,5,7]. Genetic mouse models have been valuable in studying its functions.

Loss-of-function mutations in Otulin lead to an inflammatory pathology called "OTULIN-related autoinflammatory syndrome" (ORAS) [4]. Myeloid-specific Otulin-deficient mice show that Otulin deficiency licenses RIPK3-mediated cell death in murine macrophages, leading to Nlrp3 inflammasome activation and IL-1β secretion [4]. Also, OTULIN knockdown promotes autophagy initiation but blocks autophagy maturation, as excessive ubiquitinated ATG13 protein is recruited to the phagophore, inhibiting autophagosome maturation [6].

In conclusion, Otulin is essential for regulating inflammation, cell death, and autophagy processes. Mouse models with Otulin deficiency have been instrumental in revealing its role in ORAS and associated inflammatory conditions, providing insights into the underlying mechanisms of these diseases and potential therapeutic targets [4,6].