Vmp1-KO Mouse

Vmp1, or Vacuole membrane protein 1, is an endoplasmic reticulum (ER) transmembrane protein. It plays pivotal roles in multiple cellular processes, especially in regulating autophagy, including autophagosome formation and fusion with lysosomes. It also modulates ER calcium levels, lipid droplet formation, and lipoprotein secretion [3]. Additionally, Vmp1 is involved in cellular responses against viral infections [3]. Genetic models, such as KO mouse models, have been crucial in studying its functions.

In KO mouse models, hepatocyte-specific deletion of Vmp1 severely impairs very-low-density lipoprotein (VLDL) secretion, leading to massive hepatic steatosis, hepatocyte death, inflammation, and fibrosis, hallmarks of non-alcoholic steatohepatitis (NASH) [2]. Loss of pancreatic acinar cell Vmp1 promotes inflammation, acinar-to-ductal metaplasia, and fibrosis in mice, similar to human chronic pancreatitis [4]. In the context of β-coronavirus infection, Vmp1 KO cells show impaired double-membrane vesicle (DMV) biogenesis induced by virus infection or expression of viral nonstructural proteins nsp3/4 [1].

In summary, Vmp1 is essential for maintaining cellular homeostasis, regulating autophagy, lipid metabolism, and responding to viral infections. Studies using Vmp1 KO mouse models have revealed its crucial roles in diseases like NASH and pancreatitis, providing insights into disease mechanisms and potential therapeutic targets.

References:

1. Ji, Mingming, Li, Meng, Sun, Long, Deng, Hongyu, Zhao, Yan G. 2022. VMP1 and TMEM41B are essential for DMV formation during β-coronavirus infection. In The Journal of cell biology, 221, . doi:10.1083/jcb.202112081. https://pubmed.ncbi.nlm.nih.gov/35536318/

2. Jiang, Xiaoxiao, Fulte, Sam, Deng, Fengyan, Ding, Wen-Xing, Ni, Hong-Min. 2022. Lack of VMP1 impairs hepatic lipoprotein secretion and promotes non-alcoholic steatohepatitis. In Journal of hepatology, 77, 619-631. doi:10.1016/j.jhep.2022.04.010. https://pubmed.ncbi.nlm.nih.gov/35452693/

3. Tong, Jia, Wang, Qianqian, Gao, Ziyan, Liu, Yang, Lu, Chengbiao. 2024. VMP1: a multifaceted regulator of cellular homeostasis with implications in disease pathology. In Frontiers in cell and developmental biology, 12, 1436420. doi:10.3389/fcell.2024.1436420. https://pubmed.ncbi.nlm.nih.gov/39100095/

4. Wang, Shaogui, Chao, Xiaojuan, Jiang, Xiaoxiao, Ni, Hong-Min, Ding, Wen-Xing. 2021. Loss of acinar cell VMP1 triggers spontaneous pancreatitis in mice. In Autophagy, 18, 1572-1582. doi:10.1080/15548627.2021.1990672. https://pubmed.ncbi.nlm.nih.gov/34709991/