Pla2g4c-KO Mouse

Pla2g4c, encoding cytosolic phospholipase A2-gamma (cPLA2-γ), is involved in remodeling cell membranes, producing prostaglandins, and regulating arachidonic acid metabolism pathway [2,3,6]. It is also associated with lipid droplet formation [4]. Genetic studies on its polymorphisms and mutations are valuable for understanding its functions.

A genome-wide association study found that the rs2303744 polymorphism in Pla2g4c, which causes an amino acid substitution, is associated with Multiple System Atrophy. The cPLA2γ-Ile143 isoform encoded by the MSA risk allele has decreased transacylase activity, potentially perturbing membrane phospholipids and α-synuclein biology [1]. In a murine asthma model, the Pla2g4c/COX-2 (Ptgs2)/PGD2 synthase 2 (Hpgds) axis was significantly increased in bronchial smooth muscle tissues of OA-challenged mice, and increased PGD2 might cause airway smooth muscle hyperresponsiveness [2]. Hepatitis C virus (HCV) infection upregulates Pla2g4c, which is important for HCV replication and lipid droplet formation. Both the membrane attachment and enzymatic activity of Pla2g4c are required for lipid droplet biogenesis [3,4]. Polymorphisms in Pla2g4c are associated with schizophrenia risk, illness severity in male patients, and CRC prognosis, especially in stage II disease. The rs251684 variant of Pla2g4c may be associated with autism spectrum disorder in the Northeast Han Chinese population [5,6,7].

In conclusion, Pla2g4c is essential for cell membrane remodeling, prostaglandin production, and lipid droplet formation. Genetic studies, including those on polymorphisms, have revealed its associations with multiple diseases such as Multiple System Atrophy, asthma, HCV-related diseases, schizophrenia, CRC, and autism spectrum disorder. These findings contribute to understanding the biological functions of Pla2g4c and the molecular mechanisms of these diseases.