Biomaterial Database

Mylk3 null C57BL/6N mice develop cardiomyopathy, whereas Nnt null C57BL/6J mice do not. 2020

Jack L Williams, and Anju Paudyal, and Sherine Awad, and James Nicholson, and Dominika Grzesik, and Joaquin Botta, and Eirini Meimaridou, and Avinaash V Maharaj, and Michelle Stewart, and Andrew Tinker, and Roger D Cox, and Lou A Metherell

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.

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.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008810	Mice, Inbred C57BL	One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases.	Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008822	Mice, Transgenic	Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.	Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D009202	Cardiomyopathies	A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).	Myocardial Disease,Myocardial Diseases,Myocardial Diseases, Primary,Myocardial Diseases, Secondary,Myocardiopathies,Primary Myocardial Disease,Cardiomyopathies, Primary,Cardiomyopathies, Secondary,Primary Myocardial Diseases,Secondary Myocardial Diseases,Cardiomyopathy,Cardiomyopathy, Primary,Cardiomyopathy, Secondary,Disease, Myocardial,Disease, Primary Myocardial,Disease, Secondary Myocardial,Diseases, Myocardial,Diseases, Primary Myocardial,Diseases, Secondary Myocardial,Myocardial Disease, Primary,Myocardial Disease, Secondary,Myocardiopathy,Primary Cardiomyopathies,Primary Cardiomyopathy,Secondary Cardiomyopathies,Secondary Cardiomyopathy,Secondary Myocardial Disease
D009219	Myosin-Light-Chain Kinase	An enzyme that phosphorylates myosin light chains in the presence of ATP to yield myosin-light chain phosphate and ADP, and requires calcium and CALMODULIN. The 20-kDa light chain is phosphorylated more rapidly than any other acceptor, but light chains from other myosins and myosin itself can act as acceptors. The enzyme plays a central role in the regulation of smooth muscle contraction.	Myosin Kinase,Myosin LCK,Myosin Regulatory Light-Chain Kinase,Kinase, Myosin,Kinase, Myosin-Light-Chain,LCK, Myosin,Myosin Light Chain Kinase,Myosin Regulatory Light Chain Kinase
D009250	NADP Transhydrogenases	Enzymes that catalyze the reversible reduction of NAD by NADPH to yield NADP and NADH. This reaction permits the utilization of the reducing properties of NADPH by the respiratory chain and in the reverse direction it allows the reduction of NADP for biosynthetic purposes.	NADP Transhydrogenase,Pyridine Nucleotide Transhydrogenase,Energy-Linked Transhydrogenase,NAD Transhydrogenase,NADPH NAD Transhydrogenase,NADPH Transferase,Nicotinamide Nucleotide Transhydrogenase,Energy Linked Transhydrogenase,NAD Transhydrogenase, NADPH,Nucleotide Transhydrogenase, Nicotinamide,Nucleotide Transhydrogenase, Pyridine,Transferase, NADPH,Transhydrogenase, Energy-Linked,Transhydrogenase, NAD,Transhydrogenase, NADP,Transhydrogenase, NADPH NAD,Transhydrogenase, Nicotinamide Nucleotide,Transhydrogenase, Pyridine Nucleotide,Transhydrogenases, NADP
D010641	Phenotype	The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.	Phenotypes
D004195	Disease Models, Animal	Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.	Animal Disease Model,Animal Disease Models,Disease Model, Animal
D005838	Genotype	The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.	Genogroup,Genogroups,Genotypes
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia