Nlrc3-flox Mouse

NLRC3, a member of the pattern recognition receptors nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) family, is an important regulator of innate immune system homeostasis [3,4]. It can inhibit excessive immune response in the body by influencing multiple signaling pathways, such as NF-κB, STING/TBK1, and inflammasome-related pathways. It also plays roles in cell fate regulation, like preventing proliferation, promoting apoptosis, and inhibiting pyroptosis [3].

NLRC3 deficiency promotes hypoxia-induced pulmonary hypertension development via the IKK/NF-κB p65/HIF-1α pathway. In hypoxia-induced mice models, NLRC3 knockout led to increased right ventricular systolic pressure, right ventricular hypertrophy and fibrosis. In vitro and in vivo, it promoted PASMCs proliferation, HUVECs apoptosis, migration and inflammation [1].

Myeloid-specific NLRC3 deletion in mice improved macrophage glycolysis and sepsis-induced immunosuppression, as NLRC3 was found to inhibit the binding of NF-κB p65 to NFAT5, controlling the expression of glycolytic genes and pro-inflammatory cytokines in immunosuppressive macrophages [2].

Nlrc3 knockout mice showed accelerated cutaneous wound healing, mainly due to its regulatory effects on p53 signaling. Nlrc3 was found to mediate the ubiquitination and degradation of p53 in an Hsp90-dependent manner [5].

After HTNV infection, Nlrc3-/-mice developed weight loss, renal hemorrhage, and tubule dilation, resembling human HFRS symptoms, with higher viral loads in serum, spleen, and kidney compared to wild-type mice [6].

In conclusion, NLRC3 plays a crucial role in regulating immune responses, cell proliferation, and apoptosis, and its dysregulation is associated with various diseases including pulmonary hypertension, sepsis, wound healing, and HTNV-induced renal diseases. The use of NLRC3 knockout mouse models has provided valuable insights into its functions in these disease-related biological processes, facilitating a better understanding of disease mechanisms and potential therapeutic targets.