Table 1 Representative Atg7-KO animal models

Whole body

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Viscus

Kidney

In inducible, renal tubule-specific Atg7-KO mice, the pro-fibrotic phenotype of tubular cells is induced. Meanwhile, fibrosis is down-regulated after AKI.

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Renal proximal tubule-specific Atg7-KO mice are significantly more sensitive to cisplatin-induced AKI.

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Liver

Loss of autophagic function inhibits lipid release and hepatic fibrogenesis in ATG7-interferred hepatic stellate cells.

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Intestine

The intestinal epithelial-specific ATG7 deficiency in mouse model has a negative influence on the regenerative benefit of calorie restriction, partly caused by the function of ATG7 in modulating luminal glycocholic acid, which is crucial to the self-renewal of epithelial stem cell.

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Unlike the oncogene role of ATG7 in colon cancer, the researches about inflammation-associated colon tumorigenesis in intestinal epithelial-specific Atg7-KO mice show a negative effect on tumorigenesis of colitis-associated cancer.

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Intestinal ATG7 deficiency causes intestinal dysbiosis, which leads to a suppression of tumor initiation and growth.

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Pancreas

Impaired glucose tolerance is observed in pancreatic β cell-specific Atg7-KO mice, along with the accumulation of p62, which is required for cellular homeostasis regulation.

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Researches in ATG7-deleted β-cells with both long-term and short-term HFD mouse model employed, exhibit that short-term ATG7 deletion benefits β-cell function and enhance glucose-stimulated insulin secretion, while the long-term is opposite.

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Lung

Silencing ATG7 in lung-to-lung metastasis mice can turn the reduction of tumor nodules and cancer cell metastasis caused by increasing TIMP1.

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Tissue

Adipose

In adipocyte-specific Atg7-KO mice, HFD-induced inguinal white adipose tissue hypertrophy is promoted.

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Skin

In ATG7-negative keratinocytes, autophagy induced by UVA or UVA-oxidized phospholipids is interrupted, which further causes obstructed removal of protein aggregates and oxidized phospholipids.

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Researches carried out in ATG7-inactivated epidermal keratinocytes exhibits that corneocytes on the back of mutant mice is intensified.

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ATG7 deletion in EC assists skin wound healing via promoting paracrine regulation.

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Neuron

Excitatory forebrain neurons-specific ATG7 deletion in mouse model markedly inhibits Aβ secretion, which is the pathological character of AD.

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Mitochondrial hyperfusion is found in ATG7-deficient astrocytes, which plays a key role in cell fate specification during autophagy

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Muscle

In L6 skeletal muscle cells, iron-induced ROS production accompanied by apoptosis is enhanced by ATG7 deficiency.

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VSMC-specific Atg7-KO mice suffer an elevation in aortic stiffness, and then compensatory mechanisms might be switched to maintain circulatory homeostasis.

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During the diabetic courses, AGEs are able to active vascular smooth calcification and apoptosis, which can be inhibited by ATG7 deficiency.

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Skeleton and Blood

Compared with WT mice, the osteoblasts-specific Atg7-KO ones have markedly lower relative bone formation rate. Furthermore, the interruption of autophagy causes a decrease in bone volume, thickness, stiffness, and ultimate breaking force.

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ATG7-deficient neutrophil precursors are observed to enhance glycolytic activity enhancement and lipid droplet accumulation, but impair mitochondrial respiration and reduce ATP production.

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ATG7 deletion in murine BM-MNCs has a negative effect on STAT3 activation accompanied by its nuclear translocation. ATG7-mediated autophagy can protect BM-MNCs from radiation-induced genotoxic stress.

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