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• W2116721861 abstract "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." @default.
• W2116721861 created "2016-06-24" @default.
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• W2116721861 date "2014-08-28" @default.
• W2116721861 modified "2023-09-24" @default.
• W2116721861 title "NKX2-5, a modifier of skeletal muscle pathology due to RNA toxicity" @default.
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• W2116721861 doi "https://doi.org/10.1093/hmg/ddu443" @default.
• W2116721861 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4262498" @default.
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