Genetic control of mitochondrial malic enzyme in mouse brain.

Abstract

A mitochondrial malic enzyme (EC 1.1.1.40; L-malate: NADP/sup +/ oxidoreductase (oxalacetate-decarboxylating) has been extensively purified from mouse heart and brain. The molecular weight of the enzyme was determined in the analytical ultracentrifuge to be 250,000 to 253,000. Rabbit antiserum has been prepared against the purified heart enzyme. The antiserum is specific for the mitochondrial form of malic enzyme and cross-reacts completely with the enzyme from brain. An examination of the specific activity of the enzyme in heart and brain mitochondrial pellets of 10 inbred strains showed that all had essentially identical heart activities, whereas the brain activities fell into two distinct classes. F/sub 1/ hybrid animals between a high activity strain (C3H) and a low activity strain (C57BL/10) had an exactly intermediate level of activity. Using the antiserum, it has been shown that the tissue-specific difference in the specific activity of the enzyme in brains of C3H and C57BL/10 mice is due to the presence of more enzyme molecules in one of the strains than in the other. Genetic analysis has established that the level of expression of mitochondrial malic enzyme in brain is determined by a single locus, designated Mdr, which exists in two allelic forms. Mdr alleles havemore » no effect on the expression of the enzyme in heart.« less