Genetic control of metabolism: enzyme studies of theobeseandadiposemutants in the mouse

Abstract

SUMMARY: The activity of several enzymes has been determined in the livers of homozygousobeseandadiposemice, their normal litter-mates, and phenocopies induced in normal mice by aurothioglucose (ATG) injections.Obese, adiposeand 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 wild-type. 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 roth theadandobgenes 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 inobeseandadiposemice are compared to several other enzyme activity differences reported in the literature forobesemice. These are discussed in relation to genetical criteria that may be estarlished to assess, from quantitative data, whether an enzyme is the site of the primary lesion in a mutant pheno-type. Some general observations are made on genetics and the control of metabolism.