TABLE 1.
The mutations in autophagy genes or deregulation of autophagy resulted in skeletal muscle disorders, and the mouse models with impaired autophagy pathway showed the phenotypes of abnormal skeletal muscles.
| Gene/locus | Mutation | Inheritance | Diseases | Autophagy association | Clinical features | KO mouse model |
| DMD | Deletions; Duplications; Point Mutations (PMID: 19937601) | X-linked recessive | Duchenne muscular dystrophy (DMD) | Lower levels of LC3 II and significant accumulation of p62 (PMID: 23152054) | Progressive degeneration of skeletal muscle, impaired heart and respiratory musculature | Resemble human phenotypes (PMID: 6583703; 29479480) |
| LAMP2 | Deletions; Point Mutations (PMID: 20173215; 22695892) | X-linked dominant | Danon disease | Accumulation of autophagic vacuoles (PMID: 10972293) | Heart failure, mental retardation, hypertrophic cardiomyopathy, and proximal muscle weakness | Share many similarities with human phenotypes (PMID: 10972293) |
| VMA21 | Point Mutations (PMID: 31826868) | X-linked recessive | XMEA | excessive autophagy (PMID: 23315026; 27916343) | Slowly progressive muscle weakness | Autophagic myopathy (PMID: 31826868) |
| GAA | Point Mutations (PMID: 16917947; 14695532) | Autosomal recessive | Pompe disease | Accumulation of glycogen (PMID: 14695532) | hypotonic with large hearts; muscle weakness | Identical with human (PMID: 9384603) |
| DYSF | Point mutations; Deletions; Insertions (PMID: 18853459: 27602406) | Autosomal-dominant/recessive | LGMD2B | Lipid accumulation (PMID: 24685690) | Wasting; myopathic changes | Mimic human dysferlinopathies (PMID: 23473732) |
| TRIM32 | Point Mutations (PMID: 17994549) | Autosomal recessive | LGMD2H | Bind the autophagy proteins AMBRA1 and ULK1 and stimulate ULK1 activity (PMID: 31234693) | Slowly progressive proximal muscular dystrophy | Resemble human phenotypes (PMID: 19155210) |
| ATG5 | Involved in the extension of the phagophoric membrane in autophagic vesicles (PMID: 17331981) | Small size, small muscle fibers vacuolation and occasional centrally nucleated muscle fibers (PMID: 27693508) | ||||
| ATG8 | Required for fusion of peroxisomal and vacuolar membranes (PMID: 21867568) | Accumulation of ubiquitinated (Ub) proteins and P62/SQSTM1 (PMID: 17580304) |