| First Author | Yadava RS | Year | 2008 |
| Journal | Nat Genet | Volume | 40 |
| Issue | 1 | Pages | 61-8 |
| PubMed ID | 18084293 | Mgi Jnum | J:131302 |
| Mgi Id | MGI:3773474 | Doi | 10.1038/ng.2007.28 |
| Citation | Yadava RS, et al. (2008) RNA toxicity in myotonic muscular dystrophy induces NKX2-5 expression. Nat Genet 40(1):61-8 |
| abstractText | Myotonic muscular dystrophy (DM1) is the most common inherited neuromuscular disorder in adults and is considered the first example of a disease caused by RNA toxicity. Using a reversible transgenic mouse model of RNA toxicity in DM1, we provide evidence that DM1 is associated with induced NKX2-5 expression. Transgene expression resulted in cardiac conduction defects, increased expression of the cardiac-specific transcription factor NKX2-5 and profound disturbances in connexin 40 and connexin 43. Notably, overexpression of the DMPK 3' UTR mRNA in mouse skeletal muscle also induced transcriptional activation of Nkx2-5 and its targets. In human muscles, these changes were specific to DM1 and were not present in other muscular dystrophies. The effects on NKX2-5 and its downstream targets were reversed by silencing toxic RNA expression. Furthermore, using Nkx2-5+/- mice, we show that NKX2-5 is the first genetic modifier of DM1-associated RNA toxicity in the heart. |
