Mpo KO Mouse

Myeloperoxidase (MPO), an enzyme present in neutrophil granules, plays a crucial role in the immune system by assisting neutrophils in killing bacteria and fungi through the conversion of hydrogen peroxide and chloride ions into hypochlorous acid ^[1]. However, MPO can also cause oxidative damage to host tissues. Anti-neutrophil cytoplasmic antibodies (ANCAs) are a class of autoantibodies that mistakenly target proteins within neutrophils, primarily classified into two types: pANCA targeting MPO and cANCA targeting proteinase 3 (PR3). ANCA-associated vasculitis (AAV) is a group of autoimmune diseases characterized by vascular inflammation and tissue damage, mainly including microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA) ^[2-3]. When the immune system erroneously produces antibodies against MPO (i.e., MPO-ANCA), these antibodies can bind to MPO in neutrophils, activating neutrophils and leading to vascular wall damage and inflammatory responses. The clinical manifestations of AAV patients are diverse, including symptoms such as fever, fatigue, weight loss, and kidney and lung lesions. MPO-ANCA is closely associated with MPA and is relatively less common in GPA, but approximately 60% of GPA patients also exhibit MPO-ANCA positivity ^[2-3].

This strain is an Mpo gene knockout (KO) mouse model, constructed by knocking out all protein-coding sequences of the Mpo gene (the homologous gene of human MPO) in mice using gene editing technology. Studies have shown that Mpo KO mice exhibit almost no physiological abnormalities under normal conditions and are only more susceptible to certain pathogen infections ^[4-5]. In ANCA-associated vasculitis (AAV) studies, Mpo KO mice are widely used to prepare mouse auto-MPO antibodies. The specific method involves immunizing Mpo KO mice with recombinant mouse MPO antigen as donors to produce anti-mouse MPO auto-antibodies, and then injecting the antibodies into normal mice (or target humanized mice) to induce ANCA-associated vasculitis and use them for targeted drug testing ^[6-7]. This method is the most commonly used approach in ANCA research. It has been applied to the preclinical efficacy testing of avacopan, a C5aR antagonist approved by the FDA for the treatment of ANCA ^[8].