Mylk3 null C57BL/6N mice develop cardiomyopathy, whereas Nnt null C57BL/6J mice do not

Williams, Jack L., Paudyal, Anju, Awad, Sherine, Nicholson, James, Grzesik, Dominika, Botta, Joaquin, Meimaridou, Eirini, Maharaj, Avinaash, Stewart, Michelle, Tinker, Andrew, Cox, Roger D. and Metherell, Louise A. (2020) Mylk3 null C57BL/6N mice develop cardiomyopathy, whereas Nnt null C57BL/6J mice do not. Life Science Alliance, 3 (4). pp. 1-15. ISSN 2575-1077

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Abstract / Description

The C57BL/6J and C57BL/6N mice have well-documented phenotypic and genotypic differences, including the infamous nicotinamide nucleotide transhydrogenase (Nnt) null mutation in the C57BL/6J substrain, which has been linked to cardiovascular traits in mice and cardiomyopathy in humans. To assess whether Nnt 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 (Mylk3) mutation in C57BL/6N mice, which abolishes MYLK3 protein expression. These results indicate the C57BL/6J Nnt-null mice do not develop cardiomyopathy; however, we identified a null mutation in Mylk3 as a credible cause of the cardiomyopathy phenotype in the C57BL/6N.

Item Type: Article
Uncontrolled Keywords: Mylk3 null C57BL/6N mice; Nnt null C57BL/6J mice; cardiomyopathy; nicotinamide nucleotide transhydrogenase (Nnt) null mutation
Subjects: 500 Natural Sciences and Mathematics > 570 Life sciences; biology
Department: School of Human Sciences
SWORD Depositor: Pub Router
Depositing User: Pub Router
Date Deposited: 06 Apr 2020 10:17
Last Modified: 11 Nov 2022 09:53


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