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 f or physiological variation and interpreting gene expression in terms of phe notype at the whole organism level in order to understand the pathophysiolo gy of disease. We present a novel metabonomic approach to the investigation of genetic influences on metabolic balance and metabolite excretion patter ns in two phenotypically normal mouse models (C57BL10J and Alpk:ApfCD). Che mometric techniques were applied to optimise recovery of biochemical inform ation from complex H-1 NMR urine spectra and to determine metabolic biomark er differences between the two strains. Differences were observed in tricar boxylic acid cycle intermediates and methylamine pathway activity. We sugge st here a new 'metabotype' concept, which will be of value in relating quan titative physiological and biochemical data to both phenotypic and genetic variation in animals and man, (C) 2000 Federation of European Biochemical S ocieties. Published by Elsevier Science B,V, All rights reserved.