title: Organic aciduria and butyryl CoA dehydrogenase deficiency in BALB/cByJ mice.
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 of n-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 near Bcd-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.
authors.affiliation: Department of Anatomy and Cell Biology, Georgetown University School of Medicine, Washington, D.C. 20007.
authors.forename: S P
authors.initials: SP
authors.lastname: Schiffer
authors.forename: M
authors.initials: M
authors.lastname: Prochazka
authors.forename: P F
authors.initials: PF
authors.lastname: Jezyk
authors.forename: T H
authors.initials: TH
authors.lastname: Roderick
authors.forename: M
authors.initials: M
authors.lastname: Yudkoff
authors.forename: D F
authors.initials: DF
authors.lastname: Patterson
mesh_terms: D000818:Animals; D044926:Butyryl-CoA Dehydrogenase; D003433:Crosses, Genetic; D044943:Fatty Acid Desaturases / Q000172:deficiency* / Q000235:genetics; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D014644:Genetic Variation; D005998:Glycine / Q000031:analogs & derivatives* / Q000652:urine; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics; D008297:Male; D008314:Malonates / Q000652:urine*; D051379:Mice; D008807:Mice, Inbred BALB C / Q000235:genetics*; D010641:Phenotype; D012737:Sex Factors; D013045:Species Specificity
chemical_list: D007527:Isoenzymes; D008314:Malonates; C043029:N-butyrylglycine; C038080:ethylmalonic acid; D044943:Fatty Acid Desaturases; D044926:Butyryl-CoA Dehydrogenase; D005998:Glycine