A functional analysis of mouse models of cardiac disease through metabolic profiling.
Since the completion of the human and mouse genomes, the focus in mammalian biology has been on assessing gene function. Tools are needed for assessing the phenotypes of the many mouse models that are now being generated, where genes have been "knocked out," "knocked in," or mutated, so that gene expression can be understood in its biological context. Metabolic profiling of cardiac tissue through high resolution NMR spectroscopy in conjunction with multivariate statistics has been used to classify mouse models of cardiac disease. The data sets included metabolic profiles from mouse models of Duchenne muscular dystrophy, two models of cardiac arrhythmia, and one of cardiac hypertrophy. The metabolic profiles demonstrate that the strain background is an important component of the global metabolic phenotype of a mouse, providing insight into how a given gene deletion may result in very different responses in diverse populations. Despite these differences associated with strain, multivariate statistics were capable of separating each mouse model from its control strain, demonstrating that metabolic profiles could be generated for each disease. Thus, this approach is a rapid method of phenotyping mouse models of disease.
Jones
Gareth L A H
GL
Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, United Kingdom.
Sang
Elizabeth
E
Goddard
Catharine
C
Mortishire-Smith
Russell J
RJ
Sweatman
Brian C
BC
Haselden
John N
JN
Davies
Kay
K
Grace
Andrew A
AA
Clarke
Kieran
K
Griffin
Julian L
JL
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000473:pathology; D004195:Disease Models, Animal; D016678:Genome; D006331:Heart Diseases / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D006984:Hypertrophy; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D015233:Models, Statistical; D015999:Multivariate Analysis; D020388:Muscular Dystrophy, Duchenne / Q000473:pathology; D010641:Phenotype; D013045:Species Specificity; D014018:Tissue Distribution