Table 3.
Phenotypes of tissue-specific knockout mice of ATG-related genes
| Mouse model | Target tissue/cell | Major phenotype | References |
|---|---|---|---|
| Atg5 F/F;; Nestin-Cre, Atg7 F/F; Nestin-Cre | Neural cell | Neurodegeneration; accumulation of ubiquitin and p62 | 70, 71, 80 |
| FIP200 F/F; Nestin-Cre | Neural cell | Neurodegeneration; accumulation of ubiquitin, p62 and mitochondria (more severe than Atg5/7 F/F; Nestin-Cre) | 72 |
| Atg5 F/F; Pcp2-Cre, Atg7 F/F;; Pcp2-Cre | Purkinje cell | Axonal degeneration; accumulation of p62 | 115, 116 |
| Atg5 F/F; Mx1-Cre, Atg7 F/F;; Mx1-Cre, Atg7 F/F;; Alb-Cre | Hepatocyte | Hepatic failure, hepatomegaly; accumulation of ubiquitin, p62 and mitochondria | 19, 67, 70, 80 |
| Atg5 F/F; MLC2v-Cre | Cardiomyocyte | Minimal abnormal phenotype (sensitive to pressure overload-cardiac failure) | 73 |
| Atg5 F/F; MerCreMer | Cardiomyocyte | Cardiac hypertrophy and dysfunction; accumulation of ubiquitin, p62 and mitochondria | 73 |
| Atg5 F/F; HSA-Cre | Skeletal muscle | Atrophy of fast muscle fibres; accumulation of ubiquitin and p62 | 74 |
| Atg5 F/F; Mlc1-Cre | Skeletal muscle | Muscle atrophy and weakness; accumulation of ubiquitin, p62 and mitochondria | 75 |
| Atg7 F/F; Ap2-Cre | Adipocyte | Decreased white adipose tissue mass, resistant to obesity; accumulation of p62 and mitochondria | 60, 62 |
| Atg5 F/F; EL-Cre | Pancreatic acinar cell | No abnormal phenotype (resistant to acute pancreatitis) | 117 |
| Atg7 F/F; Rip-Cre | Pancreatic β-cell | Impaired β-cell function, reduced β-cell mass; accumulation of ubiquitin, p62 and mitochondria | 76, 77 |
| Atg5 F/F; Zp3-Cre | Oocyte | Embryonic lethal at 4–8-cell stage (if fertilized with Atg5−sperm) | 11 |
| Atg5 F/F; Lck-Cre, Atg7 F/F; Lck-Cre | T cell | Decreased T-cell numbers; accumulation of mitochondria | 55, 56 |
| Atg5 F/F; CD19-Cre | B cell | Reduced B-1a B-cell numbers | 59 |
| Atg7 F/F; Vav-Cre | Haematopoietic cell | Severe anaemia, lymphopenia (T and B cells); accumulation of mitochondria | 53 |
| Atg5 F/F; CD11c-Cre | Dendritic cell | (Succumbed to viral infection due to defects in antigen presentation) | 118 |
| Atg5 F/F; Podocin-Cre | Podocyte | Late-onset glomerulosclerosis; accumulation of ubiquitin, p62 and mitochondria | 78 |
Phenotypes of tissue-specific knockout mice of ATG-related genes are listed. F, floxed allele; MLC2v, myosin light chain 2v; Mlc1, myosin light chain 1; HAS, human skeletal actin; EL, elastase I; Rip, rat insulin promoter. ‘Accumulation of ubiquitin’ refers to the accumulation of either ubiquitylated proteins or ubiquitin aggregates. ‘Accumulation of p62’ refers to the accumulation of either p62 protein or p62-positive aggregates.