Nlrp3-flox Mouse

Nlrp3, also known as NACHT, leucine-rich repeat (LRR), and pyrin domain (PYD)-containing protein 3, is a key component of the NLRP3 inflammasome. The NLRP3 inflammasome is a multi-protein signaling complex that triggers the activation of inflammatory caspases and the maturation of interleukin-1β, playing a crucial role in the innate immune response. It is involved in various biological processes and is associated with numerous human autoinflammatory, autoimmune diseases, as well as other conditions such as cancer, acute liver injury, and cardiovascular diseases [2,5,6,7].

Mitophagy/autophagy blockade leads to the accumulation of damaged, ROS-generating mitochondria, which in turn activates the NLRP3 inflammasome. Inhibition of the voltage-dependent anion channel, which dysregulates mitochondrial activity, suppresses both ROS generation and inflammasome activation, indicating that NLRP3 inflammasome senses mitochondrial dysfunction [1]. Different NLRP3 stimuli lead to the disassembly of the trans-Golgi network (TGN), and NLRP3 is recruited to the dispersed TGN through an ionic bond with phosphatidylinositol-4-phosphate (PtdIns4P), leading to its aggregation and downstream signaling activation [3]. Palmitoylation of NLRP3 Cys126 by ZDHHC7 promotes NLRP3-mediated inflammasome activation, and perturbation of this palmitoylation diminishes NLRP3 activation in macrophages and in vivo [4]. In the context of acute liver injury, aberrant activation of the NLRP3 inflammasome is involved in various types of injury, and its activation is linked to programmed cell death [6]. In cardiovascular diseases, NLRP3 is sensitive to danger signals like ischemia and alarmins, and its activation regulates cell survival through caspase-1 and gasdermin-D [7].

In conclusion, Nlrp3, as a key part of the NLRP3 inflammasome, is essential in the innate immune response and inflammation-related processes. Model-based research, especially studies using gene knockout or conditional knockout mouse models (although not specifically detailed in these abstracts but generally important in such research), has helped to reveal its role in multiple disease areas such as inflammation-related diseases, cancer, acute liver injury, and cardiovascular diseases. Understanding Nlrp3 is crucial for developing therapeutic strategies against these diseases.