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Inhibition of nonsense‐mediated mRNA decay rescues the phenotype in Ullrich's disease

2004; Wiley; Volume: 55; Issue: 5 Linguagem: Inglês

10.1002/ana.20107

1531-8249

Fusako Usuki, Akio Yamashita, Itsuro Higuchi, Tetsuo Ohnishi, Tadafumi Shiraishi, Mitsuhiro Osame, Shigeo Ohno,

Neurogenetic and Muscular Disorders Research

Abstract Nonsense‐mediated mRNA decay (NMD) is an mRNA surveillance system that eliminates aberrant mRNAs containing premature translation termination codons (PTCs). We evaluated the role of NMD in of Ullrich's disease. The patient has a frameshift mutation with a PTC in the collagen VI α2 gene causing the loss of collagen VI and functional defects in extracellular matrix (ECM). The pharmacological block of NMD caused upregulation of the mutant collagen VI α2 subunit, resulting in collagen VI assembly and partially functional ECM formation. Our results suggest that NMD inhibitors can be used as a therapeutic tool to rescue some human genetic diseases exacerbated by NMD.