{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T05:00:31Z","timestamp":1790485231945,"version":"4.1.0"},"reference-count":89,"publisher":"Life Science Alliance, LLC","issue":"4","license":[{"start":{"date-parts":[[2020,3,25]],"date-time":"2020-03-25T00:00:00Z","timestamp":1585094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015652","name":"Barts charity","doi-asserted-by":"crossref","award":["MGU0361"],"award-info":[{"award-number":["MGU0361"]}],"id":[{"id":"10.13039\/100015652","id-type":"DOI","asserted-by":"crossref"}]},{"name":"People Programme","award":["608765"],"award-info":[{"award-number":["608765"]}]},{"name":"Medical Research Council","award":["165071"],"award-info":[{"award-number":["165071"]}]},{"name":"Marie Sklodowska Curie Innovative Training Network programme","award":["721532"],"award-info":[{"award-number":["721532"]}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"crossref","award":["RG\/15\/15\/31742"],"award-info":[{"award-number":["RG\/15\/15\/31742"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Medical Research Council","award":["MC_U142661184"],"award-info":[{"award-number":["MC_U142661184"]}]},{"name":"Medical Research Council","award":["MR\/R02426X\/1"],"award-info":[{"award-number":["MR\/R02426X\/1"]}]}],"content-domain":{"domain":["life-science-alliance.org"],"crossmark-restriction":true},"short-container-title":["Life Sci. Alliance"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:p>The C57BL\/6J and C57BL\/6N mice have well-documented phenotypic and genotypic differences, including the infamous nicotinamide nucleotide transhydrogenase (<jats:italic>Nnt<\/jats:italic>) null mutation in the C57BL\/6J substrain, which has been linked to cardiovascular traits in mice and cardiomyopathy in humans. To assess whether<jats:italic>Nnt<\/jats:italic>loss alone causes a cardiovascular phenotype, we investigated the C57BL\/6N, C57BL\/6J mice and a C57BL\/6J-BAC transgenic rescuing NNT expression, at 3, 12, and 18 mo. We identified a modest dilated cardiomyopathy in the C57BL\/6N mice, absent in the two B6J substrains. Immunofluorescent staining of cardiomyocytes revealed eccentric hypertrophy in these mice, with defects in sarcomere organisation. RNAseq analysis identified differential expression of a number of cardiac remodelling genes commonly associated with cardiac disease segregating with the phenotype. Variant calling from RNAseq data identified a myosin light chain kinase 3 (<jats:italic>Mylk3<\/jats:italic>) mutation in C57BL\/6N mice, which abolishes MYLK3 protein expression. These results indicate the C57BL\/6J<jats:italic>Nnt<\/jats:italic>-null mice do not develop cardiomyopathy; however, we identified a null mutation in<jats:italic>Mylk3<\/jats:italic>as a credible cause of the cardiomyopathy phenotype in the C57BL\/6N.<\/jats:p>","DOI":"10.26508\/lsa.201900593","type":"journal-article","created":{"date-parts":[[2020,3,25]],"date-time":"2020-03-25T20:15:28Z","timestamp":1585167328000},"page":"e201900593","update-policy":"https:\/\/doi.org\/10.26508\/lsa.crossmarkpolicy","source":"Crossref","is-referenced-by-count":42,"title":["<i>Mylk3<\/i>null C57BL\/6N mice develop cardiomyopathy, whereas<i>Nnt<\/i>null C57BL\/6J mice do not"],"prefix":"10.26508","volume":"3","author":[{"given":"Jack L","family":"Williams","sequence":"first","affiliation":[{"name":"Centre for Endocrinology, William Harvey Research Institute, Charterhouse Square, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anju","family":"Paudyal","sequence":"additional","affiliation":[{"name":"Medical Research Council Harwell Institute, Mary Lyon Centre, Harwell Campus, Oxfordshire, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherine","family":"Awad","sequence":"additional","affiliation":[{"name":"Centre for Endocrinology, William Harvey Research Institute, Charterhouse Square, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Nicholson","sequence":"additional","affiliation":[{"name":"Centre for Endocrinology, William Harvey Research Institute, Charterhouse Square, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominika","family":"Grzesik","sequence":"additional","affiliation":[{"name":"Centre for Endocrinology, William Harvey Research Institute, Charterhouse Square, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6450-1267","authenticated-orcid":true,"given":"Joaquin","family":"Botta","sequence":"additional","affiliation":[{"name":"Centre for Endocrinology, William Harvey Research Institute, Charterhouse Square, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eirini","family":"Meimaridou","sequence":"additional","affiliation":[{"name":"School of Human Sciences, London Metropolitan University, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8051-3866","authenticated-orcid":true,"given":"Avinaash V","family":"Maharaj","sequence":"additional","affiliation":[{"name":"Centre for Endocrinology, William Harvey Research Institute, Charterhouse Square, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Stewart","sequence":"additional","affiliation":[{"name":"Medical Research Council Harwell Institute, Mary Lyon Centre, Harwell Campus, Oxfordshire, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Tinker","sequence":"additional","affiliation":[{"name":"William Harvey Heart Centre, William Harvey Research Institute, Charterhouse Square, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7170-5014","authenticated-orcid":true,"given":"Roger D","family":"Cox","sequence":"additional","affiliation":[{"name":"Medical Research Council Harwell Institute, Mammalian Genetics Unit, Harwell Campus, Oxfordshire, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0530-3524","authenticated-orcid":true,"given":"Lou A","family":"Metherell","sequence":"additional","affiliation":[{"name":"Centre for Endocrinology, William Harvey Research Institute, Charterhouse Square, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"12380","published-online":{"date-parts":[[2020,3,25]]},"reference":[{"key":"2020032513141393000_3.4.e201900593.1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0133132"},{"key":"2020032513141393000_3.4.e201900593.2","doi-asserted-by":"publisher","DOI":"10.1186\/1745-6150-9-18"},{"key":"2020032513141393000_3.4.e201900593.3","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddl034"},{"key":"2020032513141393000_3.4.e201900593.4","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv460"},{"key":"2020032513141393000_3.4.e201900593.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2017.06.004"},{"key":"2020032513141393000_3.4.e201900593.6","doi-asserted-by":"publisher","DOI":"10.2337\/db15-0982"},{"key":"2020032513141393000_3.4.e201900593.7","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00071.2010"},{"key":"2020032513141393000_3.4.e201900593.8","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.10.6298"},{"key":"2020032513141393000_3.4.e201900593.9","first-page":"326","article-title":"Behavioral differences among fourteen inbred mouse strains commonly used as disease models","volume":"55","author":"Bothe","year":"2005","journal-title":"Comp Med"},{"key":"2020032513141393000_3.4.e201900593.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2012.12.010"},{"key":"2020032513141393000_3.4.e201900593.11","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2299"},{"key":"2020032513141393000_3.4.e201900593.12","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-16-0056"},{"key":"2020032513141393000_3.4.e201900593.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jash.2016.12.002"},{"key":"2020032513141393000_3.4.e201900593.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2015.07.008"},{"key":"2020032513141393000_3.4.e201900593.15","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.114.04067"},{"key":"2020032513141393000_3.4.e201900593.16","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.115.001026"},{"key":"2020032513141393000_3.4.e201900593.17","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00088.2013"},{"key":"2020032513141393000_3.4.e201900593.18","doi-asserted-by":"publisher","DOI":"10.2337\/db06-0358"},{"key":"2020032513141393000_3.4.e201900593.19","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00586-4"},{"key":"2020032513141393000_3.4.e201900593.20","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-019-02257-4"},{"key":"2020032513141393000_3.4.e201900593.21","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.003145"},{"key":"2020032513141393000_3.4.e201900593.22","doi-asserted-by":"publisher","DOI":"10.1038\/srep23756"},{"key":"2020032513141393000_3.4.e201900593.23","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2013-14-7-r82"},{"key":"2020032513141393000_3.4.e201900593.24","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00274.2002"},{"key":"2020032513141393000_3.4.e201900593.25","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00592.2009"},{"key":"2020032513141393000_3.4.e201900593.26","doi-asserted-by":"publisher","DOI":"10.1172\/JCI36154"},{"key":"2020032513141393000_3.4.e201900593.27","doi-asserted-by":"publisher","DOI":"10.1097\/HCO.0000000000000512"},{"key":"2020032513141393000_3.4.e201900593.28","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.112.116202"},{"key":"2020032513141393000_3.4.e201900593.29","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvw069"},{"key":"2020032513141393000_3.4.e201900593.30","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2016.00480"},{"key":"2020032513141393000_3.4.e201900593.31","doi-asserted-by":"publisher","DOI":"10.1002\/ehf2.12410"},{"key":"2020032513141393000_3.4.e201900593.32","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-17769-1"},{"key":"2020032513141393000_3.4.e201900593.33","doi-asserted-by":"publisher","DOI":"10.1038\/nature10413"},{"key":"2020032513141393000_3.4.e201900593.34","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/15.20.8125"},{"key":"2020032513141393000_3.4.e201900593.35","doi-asserted-by":"publisher","DOI":"10.15252\/msb.20145136"},{"key":"2020032513141393000_3.4.e201900593.36","first-page":"226","article-title":"Neural network prediction of translation initiation sites in eukaryotes: Perspectives for EST and genome analysis","volume":"5","author":"Pedersen","year":"1997","journal-title":"Proc Int Conf Intell Syst Mol Biol"},{"key":"2020032513141393000_3.4.e201900593.37","doi-asserted-by":"publisher","DOI":"10.1142\/S0219720003000216"},{"key":"2020032513141393000_3.4.e201900593.38","doi-asserted-by":"publisher","DOI":"10.1159\/000486337"},{"key":"2020032513141393000_3.4.e201900593.39","doi-asserted-by":"publisher","DOI":"10.2337\/db16-0291"},{"key":"2020032513141393000_3.4.e201900593.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2013.05.049"},{"key":"2020032513141393000_3.4.e201900593.41","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2009.477"},{"key":"2020032513141393000_3.4.e201900593.42","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.730473"},{"key":"2020032513141393000_3.4.e201900593.43","doi-asserted-by":"publisher","DOI":"10.1007\/s00240-018-1040-3"},{"key":"2020032513141393000_3.4.e201900593.44","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0141130"},{"key":"2020032513141393000_3.4.e201900593.45","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19082234"},{"key":"2020032513141393000_3.4.e201900593.46","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2002.024505"},{"key":"2020032513141393000_3.4.e201900593.47","doi-asserted-by":"publisher","DOI":"10.1152\/physiologyonline.2001.16.1.5"},{"key":"2020032513141393000_3.4.e201900593.48","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.107.161687"},{"key":"2020032513141393000_3.4.e201900593.49","doi-asserted-by":"publisher","DOI":"10.1172\/JCI30804"},{"key":"2020032513141393000_3.4.e201900593.50","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1600633113"},{"key":"2020032513141393000_3.4.e201900593.51","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1242\/dev.125.10.1943","article-title":"Ventricular muscle-restricted targeting of the RXRa gene reveals a non-cell-autonomous requirement in cardiac chamber morphogenesis","volume":"125","author":"Chen","year":"1998","journal-title":"Development"},{"key":"2020032513141393000_3.4.e201900593.52","doi-asserted-by":"publisher","DOI":"10.1172\/JCI61134"},{"key":"2020032513141393000_3.4.e201900593.53","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-012-1131-1"},{"key":"2020032513141393000_3.4.e201900593.54","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(97)00321-0"},{"key":"2020032513141393000_3.4.e201900593.55","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2001.280.4.H1814"},{"key":"2020032513141393000_3.4.e201900593.56","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.111.6.2427"},{"key":"2020032513141393000_3.4.e201900593.57","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1118403109"},{"key":"2020032513141393000_3.4.e201900593.58","doi-asserted-by":"publisher","DOI":"10.1007\/s00335-012-9427-x"},{"key":"2020032513141393000_3.4.e201900593.59","doi-asserted-by":"publisher","DOI":"10.1038\/nature10163"},{"key":"2020032513141393000_3.4.e201900593.60","doi-asserted-by":"publisher","DOI":"10.1538\/expanim.58.141"},{"key":"2020032513141393000_3.4.e201900593.61","doi-asserted-by":"publisher","DOI":"10.1126\/science.1245503"},{"key":"2020032513141393000_3.4.e201900593.62","doi-asserted-by":"publisher","DOI":"10.1534\/g3.118.200194"},{"key":"2020032513141393000_3.4.e201900593.63","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0153472"},{"key":"2020032513141393000_3.4.e201900593.64","doi-asserted-by":"publisher","DOI":"10.1006\/geno.2002.6754"},{"key":"2020032513141393000_3.4.e201900593.65","doi-asserted-by":"publisher","DOI":"10.1007\/s00360-014-0830-3"},{"key":"2020032513141393000_3.4.e201900593.66","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvq111"},{"key":"2020032513141393000_3.4.e201900593.67","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00465.2013"},{"key":"2020032513141393000_3.4.e201900593.68","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-008-0570-x"},{"key":"2020032513141393000_3.4.e201900593.69","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13180"},{"key":"2020032513141393000_3.4.e201900593.70","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.12-9662"},{"key":"2020032513141393000_3.4.e201900593.71","doi-asserted-by":"publisher","DOI":"10.14806\/ej.17.1.200"},{"key":"2020032513141393000_3.4.e201900593.72","unstructured":"Babraham Bioinformatics: FastQC A quality control tool for high throughput sequence data. Available at https:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc\/. Accessed April 3, 2018."},{"key":"2020032513141393000_3.4.e201900593.73","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp120"},{"key":"2020032513141393000_3.4.e201900593.74","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbs038"},{"key":"2020032513141393000_3.4.e201900593.75","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2450"},{"key":"2020032513141393000_3.4.e201900593.76","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"2020032513141393000_3.4.e201900593.77","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2722"},{"key":"2020032513141393000_3.4.e201900593.78","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"key":"2020032513141393000_3.4.e201900593.79","doi-asserted-by":"publisher","DOI":"10.1038\/ng.806"},{"key":"2020032513141393000_3.4.e201900593.80","doi-asserted-by":"publisher","DOI":"10.1002\/0471250953.bi1110s43"},{"key":"2020032513141393000_3.4.e201900593.81","doi-asserted-by":"publisher","DOI":"10.1101\/201178"},{"key":"2020032513141393000_3.4.e201900593.82","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1754"},{"key":"2020032513141393000_3.4.e201900593.83","doi-asserted-by":"crossref","unstructured":"Mi H , Thomas P (2009) PANTHER pathway: An ontology-based pathway database coupled with data analysis tools. In Protein Networks and Pathway Analysis, Nikolsky Y , Bryant J (eds), pp 123\u2013140. Totowa, NJ: Humana Press.","DOI":"10.1007\/978-1-60761-175-2_7"},{"key":"2020032513141393000_3.4.e201900593.84","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw1138"},{"key":"2020032513141393000_3.4.e201900593.85","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(87)90021-2"},{"key":"2020032513141393000_3.4.e201900593.86","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-420037-1.00019-1"},{"key":"2020032513141393000_3.4.e201900593.87","doi-asserted-by":"publisher","DOI":"10.1101\/pdb.prot4986"},{"key":"2020032513141393000_3.4.e201900593.88","unstructured":"Masson\u2019s trichrome staining protocol for collagen fibers. Available at http:\/\/www.ihcworld.com\/_protocols\/special_stains\/masson_trichrome.htm. Accessed April 3, 2018."},{"key":"2020032513141393000_3.4.e201900593.89","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1318"}],"container-title":["Life Science Alliance"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.26508\/lsa.201900593","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T14:09:31Z","timestamp":1704895771000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.life-science-alliance.org\/lookup\/doi\/10.26508\/lsa.201900593"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,25]]},"references-count":89,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,3,25]]},"published-print":{"date-parts":[[2020,4]]}},"alternative-id":["10.26508\/lsa.201900593"],"URL":"https:\/\/doi.org\/10.26508\/lsa.201900593","relation":{},"ISSN":["2575-1077"],"issn-type":[{"value":"2575-1077","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,25]]}}}