An NMR-based metabonomic approach to investigate the biochemical consequences of genetic strain differences: application to the C57BL10J and Alpk:ApfCD mouse

As the human genome sequencing projects near completion, there is an active search for technologies that can provide insights into the genetic basis for physiological variation and interpreting gene expression in terms of phenotype at the whole organism level in order to understand the pathophysiology of disease. We present a novel metabonomic approach to the investigation of genetic influences on metabolic balance and metabolite excretion patterns in two phenotypically normal mouse models (C57BL10J and Alpk:ApfCD). Chemometric techniques were applied to optimise recovery of biochemical information from complex (1)H NMR urine spectra and to determine metabolic biomarker differences between the two strains. Differences were observed in tricarboxylic acid cycle intermediates and methylamine pathway activity. We suggest here a new 'metabotype' concept, which will be of value in relating quantitative physiological and biochemical data to both phenotypic and genetic variation in animals and man.