Yue-Bei Luo, Chalermchai Mitrpant, Abbie M. Adams, Russell D. Johnsen, Sue Fletcher, Frank L. Mastaglia, Steve D. Wilton
Abstract:We sought to use splice-switching antisense oligonucleotides to produce a model of accelerated ageing by enhancing expression of progerin, translated from a mis-spliced lamin A gene (LMNA) transcript in human myogenic cells. The progerin transcript (LMNA Δ150) lacks the last 150 bases of exon 11, and is translated into a truncated protein associated with the severe premature ageing disease, Hutchinson-Gilford progeria syndrome (HGPS). HGPS arises from de novo mutations that activate a cryptic splice site in ex…
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