Vmp1-flox Mouse

Vmp1, also known as Vacuole membrane protein 1, is an endoplasmic reticulum (ER) transmembrane protein. It plays a pivotal role in multiple cellular processes, especially in regulating autophagy, lipid metabolism, and organelle biogenesis [4]. Vmp1 is involved in autophagosome formation, regulating the cross-membrane phosphatidylserine (PS) distribution, and modulating ER calcium levels, which are essential for maintaining cellular homeostasis [2,4,5].

In gene knockout studies, Vmp1 KO cells showed impaired double-membrane vesicle (DMV) formation during β-coronavirus infection, as the zippered ER failed to close into DMVs [1]. Hepatocyte-specific deletion of Vmp1 in mice severely impaired very-low-density lipoprotein (VLDL) secretion, leading to massive hepatic steatosis, hepatocyte death, inflammation, and fibrosis, hallmarks of non-alcoholic steatohepatitis (NASH) [3]. Pancreatic acinar cell-specific vmp1 deletion in mice promoted inflammation, acinar-to-ductal metaplasia, and fibrosis, sharing histological similarities with human chronic pancreatitis (CP) [6].

In conclusion, Vmp1 is crucial for autophagy, lipid metabolism, and organelle biogenesis. Studies using Vmp1 KO mouse models have revealed its significance in diseases such as NASH and CP, providing insights into the underlying molecular mechanisms and potential therapeutic targets.