RT Journal Article
SR Electronic
T1 <em>Mylk3</em> null C57BL/6N mice develop cardiomyopathy, whereas <em>Nnt</em> null C57BL/6J mice do not
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e201900593
DO 10.26508/lsa.201900593
VO 3
IS 4
A1 Williams, Jack L
A1 Paudyal, Anju
A1 Awad, Sherine
A1 Nicholson, James
A1 Grzesik, Dominika
A1 Botta, Joaquin
A1 Meimaridou, Eirini
A1 Maharaj, Avinaash V
A1 Stewart, Michelle
A1 Tinker, Andrew
A1 Cox, Roger D
A1 Metherell, Lou A
YR 2020
UL https://www.life-science-alliance.org/content/3/4/e201900593.abstract
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.