Mzb1-KO Mouse

MZB1, also known as Marginal zone B and B-1 cell-specific protein 1, is an endoplasmic reticulum-resident protein preferentially expressed in plasma cells, marginal zone and B1 B cells [3]. It plays a crucial role in the humoral immune response, promoting the secretion of IgM and IgA by interacting with the tail piece of their heavy chains [3]. It also affects cellular processes like proliferation, apoptosis, and mitochondrial function, and is associated with pathways such as PI3K-Akt [1].

In gene-knockout related studies, Mzb1-/-mice showed increased CRC development and progression, associated with reduced intestinal IgA levels, altered gut flora, and more severe gut and systemic inflammation, indicating MZB1-mediated IgA secretion suppresses CRC triggered by gut inflammation [2]. In atherosclerotic plaque vulnerability study, downregulation of Mzb1 in mouse models increased ox-LDL-induced apoptosis and cholesterol levels in human vascular smooth muscle cells, while Mzb1 overexpression alleviated these effects and attenuated atherosclerotic plaque vulnerability [4]. In myocardial infarction mouse models, Mzb1 expression was reduced in the infarct myocardium. Knockdown of Mzb1 in neonatal mouse ventricular cardiomyocytes decreased mitochondrial membrane potential and promoted apoptosis, while overexpression improved mitochondrial function and inhibited apoptosis [5].

In conclusion, MZB1 is essential for immunoglobulin secretion, cellular proliferation, apoptosis regulation, and mitochondrial function. Gene-knockout mouse models have revealed its significant role in diseases such as colorectal cancer, atherosclerosis, and myocardial infarction, helping to understand the biological functions and disease mechanisms related to MZB1, which may provide potential therapeutic targets for these diseases.