| First Author | Gladman JT | Year | 2015 |
| Journal | Hum Mol Genet | Volume | 24 |
| Issue | 1 | Pages | 251-64 |
| PubMed ID | 25168381 | Mgi Jnum | J:216510 |
| Mgi Id | MGI:5608932 | Doi | 10.1093/hmg/ddu443 |
| Citation | Gladman JT, et al. (2015) NKX2-5, a modifier of skeletal muscle pathology due to RNA toxicity. Hum Mol Genet 24(1):251-64 |
| abstractText | RNA toxicity is implicated in a number of disorders; especially those associated with expanded repeat sequences, such as myotonic dystrophy (DM1). Previously, we have shown increased NKX2-5 expression in RNA toxicity associated with DM1. Here, we investigate the relationship between NKX2-5 expression and muscle pathology due to RNA toxicity. In skeletal muscle from mice with RNA toxicity and individuals with DM1, expression of Nkx2-5 or NKX2-5 and its downstream targets are significantly correlated with severity of histopathology. Using C2C12 myoblasts, we show that over-expression of NKX2-5 or mutant DMPK 3'UTR results in myogenic differentiation defects, which can be rescued by knockdown of Nkx2-5, despite continued toxic RNA expression. Furthermore, in a mouse model of NKX2-5 over-expression, we find defects in muscle regeneration after induced damage, similar to those seen in mice with RNA toxicity. Using mouse models of Nkx2-5 over-expression and depletion, we find that NKX2-5 levels modify disease phenotypes in mice with RNA toxicity. |
