| First Author | Ho TH | Year | 2005 |
| Journal | Hum Mol Genet | Volume | 14 |
| Issue | 11 | Pages | 1539-47 |
| PubMed ID | 15843400 | Mgi Jnum | J:99370 |
| Mgi Id | MGI:3582035 | Doi | 10.1093/hmg/ddi162 |
| Citation | Ho TH, et al. (2005) Transgenic mice expressing CUG-BP1 reproduce splicing mis-regulation observed in myotonic dystrophy. Hum Mol Genet 14(11):1539-47 |
| abstractText | Myotonic dystrophy type I (DM1) is an RNA-mediated disease caused by a non-coding CTG repeat expansion. A key feature of the RNA-mediated pathogenesis model for DM is the disrupted splicing of specific pre-mRNA targets. A link has been established between splicing regulation by CUG-BP1, a member of the CELF family of proteins, and DM1 pathogenesis. To determine whether increased CUG-BP1 function was sufficient to model DM, transgenic mice overexpressing CUG-BP1 (MCKCUG-BP1) in heart and skeletal muscle, two tissues affected in DM1, were generated. Histological and electron microscopic analyses of skeletal muscle reveal common pathological features with DM tissues: chains of central nuclei, degenerating fibers and centralized NADH reactivity. MCKCUG-BP1 mice have disrupted splicing of three CELF target pre-mRNAs, cardiac troponin T (Tnnt2), myotubularin-related 1 gene (Mtmr1) and the muscle-specific chloride channel (Clcn1), consistent with that observed in DM heart and skeletal muscle. The results are consistent with a mechanism for DM pathogenesis in which expanded repeats result in increased CUG-BP1 activity and/or other CELF family members and have trans-dominant effects on specific pre-mRNA targets. |
