Mpeg1-KO Mouse

Mpeg1, also known as Perforin-2, is a pore-forming protein encoded by the macrophage-expressed gene 1. It belongs to the Membrane Attack Complex/Perforin (MACPF) branch of the MACPF/Cholesterol Dependent Cytolysin (CDC) superfamily. Mpeg1 is highly expressed in macrophages and other phagocytes, and is postulated to play a role in immunity, with its expression upregulated in response to pro-inflammatory signals [2].

Some studies using Mpeg1 knockout mice showed conflicting results. Initially, Mpeg1tm1Pod homozygous mutant mice were reported to succumb to bacterial infection and have deficiencies in bacterial killing in vitro [1]. However, mice homozygous for the new allele Mpeg1tm1.1Pib were not abnormally susceptible to bacterial or viral infection, and showed no perturbation in bacterial killing in vitro [1]. Other research indicated that Mpeg1 -deficient mice had increased susceptibility to microbial infection, with Mpeg1 -knockout mice suffering higher mortality rates when challenged with gram-negative or-positive pathogens [3,4]. Also, in humans, germline mutations in Mpeg1 have been associated with recurrent pulmonary mycobacterial infections and persistent polymicrobial skin and soft tissue infections [2,3]. Moreover, Mpeg1 -deficient mice failed to efficiently prime CD8+ T cells to cell-associated antigens, revealing its role in cytosolic entry of antigens during cross-presentation [5].

In conclusion, Mpeg1 is likely an intracellular pore-forming immune effector. Its role in antibacterial and antiviral immunity remains somewhat controversial, but it may play a role in antigen presentation and is clearly important in the context of certain human infections, such as pulmonary mycobacterial and skin and soft tissue infections. Studies on Mpeg1 knockout mouse models have been crucial in understanding its functions in these biological processes and disease conditions [1-2,4-5,9].