Atg7, an essential autophagy-related protein, acts as an E1-like activating enzyme facilitating LC3-phosphatidylethanolamine and ATG12 conjugation. It stands at the center of two ubiquitin-like systems involved in autophagic vesicle expansion. Atg7 is crucial for classical degradative macroautophagy and also participates in regulating cell cycle, apoptosis, immunity, and protein secretion. Genetic models, such as gene knockout mouse models, have been pivotal in studying its functions [3,6].

In adipose-selective fto knockout mice, FTO deficiency decreased white fat mass and impaired ATG7-dependent autophagy, indicating that m6A mRNA methylation controls autophagy and adipogenesis by targeting Atg7 [1]. In endothelial cell-specific atg7 knockout (atg7 KO) mice, ablation of Atg7 inhibited ischemia-induced angiogenesis by upregulating Stat1, which suppresses Hif1a expression [2]. Endothelial depletion of Atg7 in Atg7-ECKO mice led to astrocyte-microvascular disassociation and BBB leakage due to down-regulation of fibronectin expression [4]. Also, neural-specific atg7 deletion in mice causes neurodegeneration, and identification of pathogenic, biallelic ATG7 variants in patients demonstrated its importance in human neural integrity [5].

In conclusion, Atg7 is essential for autophagy and plays significant roles in adipogenesis, angiogenesis, blood-brain barrier integrity, and neural development. Gene knockout mouse models have been instrumental in uncovering these functions, contributing to our understanding of diseases like obesity, cardiovascular diseases, and neurodegeneration [1,2,4,5].