Vps4a-KO Mouse

Vps4a, vacuolar-protein-sorting-associated protein 4A, is a member of the large family of AAA+ ATPases. It is a crucial component of the endosomal sorting complex required for transport (ESCRT) system, driving membrane remodeling in multiple cellular processes such as receptor degradation, cell division, and neural pruning [4]. It also has functions in regulating autophagy, lipophagy, and is involved in exosome-related processes [1,2,5].

In cardiomyocyte-specific Vps4a knockout mice, there was autophagosome accumulation, blocked autophagic flux, resulting in hypertrophic cardiomyopathy and early lethality, indicating Vps4a's role in autophagic flux regulation in cardiomyocytes [3]. In human studies, de novo missense variants in Vps4A caused multisystem disease with abnormal neurodevelopment, affecting various cellular processes like endosomal morphology, centrosome number regulation, and cell cycle progression [6]. Also, mutations in Vps4A led to syndromic congenital dyserythropoietic anemia due to cytokinesis and trafficking defects [7].

In conclusion, Vps4a is essential for membrane remodeling, autophagy, lipophagy, and exosome-related functions. The use of Vps4a knockout mouse models has revealed its significance in heart diseases such as hypertrophic cardiomyopathy, as well as in human disorders including abnormal neurodevelopment and congenital dyserythropoietic anemia. These studies help in understanding the underlying mechanisms of these diseases and may contribute to the development of new therapeutic strategies.