hPLA2G7-R92H Mouse

The PLA2G7 gene encodes a secreted enzyme known as lipoprotein-associated phospholipase A2 (Lp-PLA2) or platelet-activating factor acetylhydrolase (PAF-AH). This enzyme functions as a calcium-independent phospholipase that primarily catalyzes the degradation of platelet-activating factor (PAF) into inactive products and hydrolyzes oxidatively truncated phospholipids, thereby regulating inflammatory and oxidative stress responses ^[1]. Though it is expressed at low levels across many tissues, the gene is significantly enriched in lymphoid tissues and the placenta, and it is notably produced by inflammatory cells such as macrophages, monocytes, and mast cells. Within the circulatory system, the protein primarily associates with low-density lipoprotein (LDL) particles, where its activity is a well-recognized biomarker for atherosclerosis and coronary artery disease ^[2]. Beyond cardiovascular conditions, dysregulation or genetic defects in PLA2G7 are associated with PAF acetylhydrolase deficiency, asthma, atopy, and various malignancies-including prostate, breast, and renal cancers-where it often serves as a prognostic marker for metastasis and immunosuppressive tumor environments ^[3]. The R92H mutation (rs1805017) in the PLA2G7 gene is a non-synonymous polymorphism, which has been significantly associated with increased enzymatic activity and higher mass of the encoded Lp-PLA2 protein. Clinical studies consistently indicate that carriers of this variant face a heightened risk of coronary artery disease and clinical atherosclerosis, as the elevated enzyme activity promotes the release of pro-inflammatory mediators within vascular lesions ^[4].

The hPLA2G7-R92H is a mouse Pla2g7 gene humanized model carrying the R92H mutation constructed through gene-editing technology, in which the region from position p.F22 to partial intron 2 of the mouse Pla2g7 gene is replaced with the Mutant Human PLA2G7 CDS-rBG pA cassette. The murine signal peptide is retained. This model can be used for research on coronary artery disease (CAD) and clinical atherosclerosis, as well as for the development of PLA2G7-targeted therapeutics.