| First Author | Li D | Year | 2021 |
| Journal | Autophagy | Volume | 17 |
| Issue | 9 | Pages | 2576-2585 |
| PubMed ID | 33794726 | Mgi Jnum | J:372876 |
| Mgi Id | MGI:8250357 | Doi | 10.1080/15548627.2021.1911549 |
| Citation | Li D, et al. (2021) ATG14 and RB1CC1 play essential roles in maintaining muscle homeostasis. Autophagy 17(9):2576-2585 |
| abstractText | Defects in macroautophagy/autophagy are implicated in the pathogenesis of neuromuscular and heart diseases. To precisely define the roles of autophagy-related genes in skeletal and cardiac muscles, we generated muscle-specific rb1cc1- and atg14-conditional knockout (cKO) mice by using Ckm/Ckmm2-Cre and compared their phenotypes to those of ulk1 ulk2-conditional double-knockout (cDKO) mice. atg14-cKO mice developed hypertrophic cardiomyopathy, which was associated with abnormal accumulation of autophagic cargoes in the heart and early mortality. Skeletal muscles of both atg14-cKO and rb1cc1-cKO mice showed features of autophagic vacuolar myopathy with ubiquitin(+) SQSTM1(+) deposits, but only those of rb1cc1-cKO mice showed TARDBP/TDP-43(+) pathology and other features of the inclusion body myopathy-like disease we previously described in ulk1 ulk2-cDKO mice. Herein, we highlight tissue-specific differences between skeletal and cardiac muscles in their reliance on core autophagy proteins and unique roles for ULK1-ULK2 and RB1CC1 among these proteins in the development of TARDBP(+) pathology.ABBREVIATIONS:AVM: autophagic vacuolar myopathy; cDKO: conditional double knockout; cKO: conditional knockout; H&E: hematoxylin and eosin; IBM: inclusion body myopathy; mtDNA: mitochondrial DNA; PFA: paraformaldehyde; RNP: ribonucleoprotein; TBST: Tris-buffered saline with 0.2% Triton X-100. |
