Gpat4-flox Mouse

Gpat4, glycerol-3-phosphate acyltransferase 4, is an endoplasmic reticulum membrane-anchored protein. It plays a crucial role in glycerophospholipid biosynthesis and is involved in multiple biological pathways. In plants, it contributes to the biosynthesis of extracellular lipids like suberin and cuticular wax. In mammals, it is related to lipid metabolism, endocardial development, and the regulation of autophagy [1,2,3,4,5].

In mouse models, Gpat4 global and tissue-specific knockout mice have been used to study its function. Deficiency of Gpat4 in endocardial cells provokes endoplasmic reticulum stress response, enhances ER-mitochondrial communications, leading to mitochondrial DNA escape and triggering the cGAS-STING pathway, which affects heart development [2]. Gpat4 -/- mice also show differences in energy metabolism, with increased metabolic rate and core body temperature, and enhanced fatty acid oxidation in brown adipose tissue [6]. In vascular smooth muscle cells, saturated fatty acids are accumulated as saturated lysophosphatidic acids possibly synthesized through GPAT4, causing abnormal formation of omegasomes and inhibition of autophagic flux [4].

In conclusion, Gpat4 is essential for maintaining endoplasmic reticulum homeostasis, regulating lipid metabolism, and influencing autophagy. The use of Gpat4 knockout mouse models has provided insights into its role in heart development, energy metabolism, and vascular calcification, which may contribute to understanding and treating related diseases.