Mpo Knockout mouse models

Mpo, the mouse ortholog of human MPO, encodes myeloperoxidase, the dominant protein of neutrophil azurophilic granules, synthesized as a glycosylated precursor and processed into a disulfide linked homodimer of heavy and light chains each holding a covalently bound heme. Using hydrogen peroxide generated by NADPH oxidase, it oxidizes chloride to hypochlorous acid and tyrosine to reactive radicals, producing the 3-chlorotyrosine footprint of oxidative host defense and contributing to neutrophil extracellular trap formation and lipoprotein modification in atherosclerosis. Two translational asymmetries shape design. Human MPO deficiency is comparatively common yet clinically mild, while myeloperoxidase is the principal autoantigen of ANCA associated microscopic polyangiitis, and mouse neutrophils carry substantially less enzyme than human cells, which blunts murine oxidative readouts. Nulls suit host defense and vasculitis initiation questions, catalytically inactive knockins separate enzymatic from antigenic roles, and humanization is the appropriate allele for autoantibody epitope mapping and inhibitor programs.

Mpo null animals are straightforward to genotype and phenotype when survival is acceptable. They remain a standard background for pharmacology, biomarker, and rescue studies.