{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Song W"],"funding":["British Heart Foundation"],"pagination":["27582-93"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3149350"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["286(31)"],"pubmed_abstract":["We generated a transgenic mouse model expressing the apical hypertrophic cardiomyopathy-causing mutation ACTC E99K at 50% of total heart actin and compared it with actin from patients carrying the same mutation. The actin mutation caused a higher Ca(2+) sensitivity in reconstituted thin filaments measured by in vitro motility assay (2.3-fold for mice and 1.3-fold for humans) and in skinned papillary muscle. The mutation also abolished the change in Ca(2+) sensitivity normally linked to troponin I phosphorylation. MyBP-C and troponin I phosphorylation levels were the same as controls in transgenic mice and human carrier heart samples. ACTC E99K mice exhibited a high death rate between 28 and 45 days (48% females and 22% males). At 21 weeks, the hearts of the male survivors had enlarged atri"],"journal":["The Journal of biological chemistry"],"pubmed_title":["Molecular mechanism of the E99K mutation in cardiac actin (ACTC Gene) that causes apical hypertrophy in man and mouse."],"pmcid":["PMC3149350"],"funding_grant_id":["PS/02/002/14893","RG/07/004/22659","PG/08/077/25587"],"pubmed_authors":["Nowak K","Dyer E","Redwood CS","Copeland O","Marston SB","Tremoleda JL","Bayliss C","Wilkinson R","Harding SE","Clarke K","Leung MC","Schneider MD","Wells D","Stuckey DJ","Messer A","Song W","Monserrat L"],"additional_accession":[]},"is_claimable":false,"name":"Molecular mechanism of the E99K mutation in cardiac actin (ACTC Gene) that causes apical hypertrophy in man and mouse.","description":"We generated a transgenic mouse model expressing the apical hypertrophic cardiomyopathy-causing mutation ACTC E99K at 50% of total heart actin and compared it with actin from patients carrying the same mutation. The actin mutation caused a higher Ca(2+) sensitivity in reconstituted thin filaments measured by in vitro motility assay (2.3-fold for mice and 1.3-fold for humans) and in skinned papillary muscle. The mutation also abolished the change in Ca(2+) sensitivity normally linked to troponin I phosphorylation. MyBP-C and troponin I phosphorylation levels were the same as controls in transgenic mice and human carrier heart samples. ACTC E99K mice exhibited a high death rate between 28 and 45 days (48% females and 22% males). At 21 weeks, the hearts of the male survivors had enlarged atri","dates":{"release":"2011-01-01T00:00:00Z","publication":"2011 Aug","modification":"2025-04-21T13:56:01.899Z","creation":"2019-03-27T03:07:42Z"},"accession":"S-EPMC3149350","cross_references":{"pubmed":["21622575"],"doi":["10.1074/jbc.m111.252320","10.1074/jbc.M111.252320"]}}