| First Author | Doe J | Year | 2017 |
| Journal | Hum Mol Genet | Volume | 26 |
| Issue | 8 | Pages | 1458-1464 |
| PubMed ID | 28175314 | Mgi Jnum | J:241883 |
| Mgi Id | MGI:5903815 | Doi | 10.1093/hmg/ddx048 |
| Citation | Doe J, et al. (2017) PTRH2 gene mutation causes progressive congenital skeletal muscle pathology. Hum Mol Genet 26(8):1458-1464 |
| abstractText | Peptidyl-tRNA hydrolase 2 (PTRH2) regulates integrin-mediated pro-survival and apoptotic signaling. PTRH2 is critical in muscle development and regulates myogenic differentiation. In humans a biallelic mutation in the PTRH2 gene causes infantile-onset multisystem disease with progressive muscle weakness. We report here that the Ptrh2 knockout mouse model recapitulates the progressive congenital muscle pathology observed in patients. Ptrh2 null mice demonstrate multiple degenerating and regenerating muscle fibers, increased central nuclei, elevated creatine kinase activity and endomysial fibrosis. This progressive muscle pathology resembles the muscular dystrophy phenotype in humans and mice lacking the alpha7 integrin. We demonstrate that in normal muscle Ptrh2 associates in a complex with the alpha7beta1 integrin at the sarcolemma and Ptrh2 expression is decreased in alpha7 integrin null muscle. Furthermore, Ptrh2 expression is altered in skeletal muscle of classical congenital muscular dystrophy mouse models. Ptrh2 levels were up-regulated in dystrophin deficient mdx muscle, which correlates with the elevated levels of the alpha7beta1 integrin observed in mdx muscle and Duchenne muscular dystrophy patients. Similar to the alpha7 integrin, Ptrh2 expression was decreased in laminin-alpha2 dyW null gastrocnemius muscle. Our data establishes a PTRH2 mutation as a novel driver of congenital muscle degeneration and identifies a potential novel target to treat muscle myopathies. |
