Abstract
A metabolic screening program of inbred strains of mice has detected a marked organic aciduria in the BALB/cByJ strain. Gas chromatographic and mass spectrometric analysis identified large quantities ofn-butyrylglycine plus lesser quantities of ethylmalonic acid. Crosses with the nonexcreting C57BL/6J strain indicate that this condition is inherited as an autosomal recessive trait. Independently from this screening a variant with no detectable enzyme activity of butyryl CoA dehydrogenase (BCD) in liver and kidney of the BALB/cByJ strain but not other BALB/c sublines was discovered. Data from a three-point cross indicated that the null variant maps to the structural locus for the enzyme,Bcd-1, on chromosome 5. The findings indicate that a mutation at or nearBcd-1 in the BALB/cByJ strain resulted in a biochemical abnormality manifest as the BCD deficiency. It is concluded that accumulation of butyryl CoA due to a block in the oxidation of short-chain fatty acids results in an overproduction of organic metabolites leading to the observed organic aciduria. The fact that other BALB/c substrains do not exhibit this abnormality further suggests that this disorder reflects subline divergence within the BALB/c family.
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This work was supported by NIH Grants RR02512 and GM32592 to the University of Pennsylvania and HD23168, NS17752, and HD08536 to the Children's Hospital of Philadelphia, National Science Foundation Grant BSR 84-18828 to The Jackson Laboratory, and a Postdoctoral Fellowship from the Juvenile Diabetes Foundation International to Dr. Prochazka.
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Schiffer, S.P., Prochazka, M., Jezyk, P.F. et al. Organic aciduria and butyryl CoA dehydrogenase deficiency in BALB/cByJ mice. Biochem Genet 27, 47–58 (1989). https://doi.org/10.1007/BF00563017
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DOI: https://doi.org/10.1007/BF00563017