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Infantile neuronal ceroid lipofuscinosis (<jats:styled-content style=\"fixed-case\">INCL<\/jats:styled-content>), a childhood neurodegenerative disease, results from mutations in the <jats:italic><jats:styled-content style=\"fixed-case\">CLN<\/jats:styled-content>1<\/jats:italic> gene encoding the lysosomal enzyme, palmitoyl\u2010protein thioesterase 1 (<jats:styled-content style=\"fixed-case\">PPT<\/jats:styled-content>1) [<jats:italic>Biochim Biophys Acta <\/jats:italic><jats:bold>1832<\/jats:bold> (2013) 1806, <jats:italic>Hum Mutat<\/jats:italic> (2012) 63, <jats:italic>Biochim Biophys Acta <\/jats:italic><jats:bold>1832<\/jats:bold> (2013) 1881]. The nonsense mutation p.R151X is the most common disease\u2010causing <jats:italic><jats:styled-content style=\"fixed-case\">CLN<\/jats:styled-content>1<\/jats:italic> mutation <jats:italic>Hum Mutat<\/jats:italic> (2012) 63. In the novel <jats:italic>Cln1<\/jats:italic><jats:sup><jats:italic>R151X<\/jats:italic><\/jats:sup> mouse model of <jats:styled-content style=\"fixed-case\">INCL<\/jats:styled-content>, we found large, tissue\u2010specific variations in <jats:italic>Cln1<\/jats:italic><jats:sup><jats:italic>R151X<\/jats:italic><\/jats:sup> <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> level and <jats:styled-content style=\"fixed-case\">PPT<\/jats:styled-content>1 residual enzyme activity. These tissue\u2010specific differences strongly influenced the read\u2010through efficiency of ataluren (<jats:styled-content style=\"fixed-case\">PTC<\/jats:styled-content>124), a well\u2010known nonsense suppression drug. A two\u2010day treatment with ataluren (10 mg\/kg) increased <jats:styled-content style=\"fixed-case\">PPT<\/jats:styled-content>1 enzyme activity in the liver and muscle, but not in any other tissue examined. Our study identifies a new challenge\/hurdle for read\u2010through drug therapy: variable efficiency of read\u2010through therapy in the different tissues\/organs because of tissue\u2010specific variations in nonsense mutant transcript levels.<\/jats:p>","DOI":"10.1111\/jcmm.12744","type":"journal-article","created":{"date-parts":[[2015,12,9]],"date-time":"2015-12-09T15:39:58Z","timestamp":1449675598000},"page":"381-385","source":"Crossref","is-referenced-by-count":27,"title":["Tissue\u2010specific variation in nonsense mutant transcript level and drug\u2010induced read\u2010through efficiency in the <i>Cln1<\/i><sup><i>R151X<\/i><\/sup> mouse model of <scp>INCL<\/scp>"],"prefix":"10.1111","volume":"20","author":[{"given":"Vaughn","family":"Thada","sequence":"first","affiliation":[{"name":"Department of Biology Augustana College Sioux Falls SD USA"},{"name":"Sanford Children's Health Research Center Sanford Research Sioux Falls SD 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