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

Autor:	Williams JL; 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., Paudyal A; Medical Research Council Harwell Institute, Mary Lyon Centre, Harwell Campus, Oxfordshire, UK., Awad S; 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., Nicholson J; 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., Grzesik D; 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., Botta J; 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., Meimaridou E; School of Human Sciences, London Metropolitan University, London, UK., Maharaj AV; 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., Stewart M; Medical Research Council Harwell Institute, Mary Lyon Centre, Harwell Campus, Oxfordshire, UK., Tinker A; 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., Cox RD; Medical Research Council Harwell Institute, Mammalian Genetics Unit, Harwell Campus, Oxfordshire, UK., Metherell LA; 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 l.a.metherell@qmul.ac.uk.
Jazyk:	angličtina
Zdroj:	Life science alliance [Life Sci Alliance] 2020 Mar 25; Vol. 3 (4). Date of Electronic Publication: 2020 Mar 25 (Print Publication: 2020).
DOI:	10.26508/lsa.201900593
Abstrakt:	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. (© 2020 Williams et al.)
Databáze:	MEDLINE
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