PT  - JOURNAL ARTICLE
AU  - Williams, Jack L
AU  - Paudyal, Anju
AU  - Awad, Sherine
AU  - Nicholson, James
AU  - Grzesik, Dominika
AU  - Botta, Joaquin
AU  - Meimaridou, Eirini
AU  - Maharaj, Avinaash V
AU  - Stewart, Michelle
AU  - Tinker, Andrew
AU  - Cox, Roger D
AU  - Metherell, Lou A
TI  - <em>Mylk3</em> null C57BL/6N mice develop cardiomyopathy, whereas <em>Nnt</em> null C57BL/6J mice do not
AID  - 10.26508/lsa.201900593
DP  - 2020 Apr 01
TA  - Life Science Alliance
PG  - e201900593
VI  - 3
IP  - 4
4099  - https://www.life-science-alliance.org/content/3/4/e201900593.short
4100  - https://www.life-science-alliance.org/content/3/4/e201900593.full
SO  - Life Sci. Alliance2020 Apr 01; 3
AB  - 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.