Genetic control of metabolism: enzyme studies of the obese and adipose mutants in the mouse.

The activity of several enzymes has been determined in the livers of homozygous obese and adipose mice, their normal litter-mates, and phenocopies induced in normal mice by aurothioglucose (ATG) injections. Obese, adipose and ATG mice had higher activities of ATP citrate lyase, malic enzyme (NADP malate dehydrogenase) and pyruvate kinase than normal mice. Heterozygote activities are indistinguishable from wildtype. There was no difference between normal and fat litter-mates in the activity of malate dehydrogenase (NAD-linked), lactate dehydrogenase, isocitrate dehydrogenase and fumarase. Crosses between mice doubly heterozygous for both the ad and ob genes produced offspring that were only ' fat' or ' normal' and no offspring could be phenotypically recognized as the double mutant, either physically or in terms of ATP citrate lyase activity. Gas-liquid chromatography of the fatty acids of the depot fat showed no differences between any of the types of litter-mate. The alterations found in enzyme activity in obese and adipose mice are compared to several other enzyme activity differences reported in the literature for obese mice. These are discussed in relation to genetical criteria that may be established to assess, from quantitative data, whether an enzyme is the site of the primary lesion in a mutant phenotype. Some general observations are made on genetics and the control of metabolism.

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