Gestational, pathologic and biochemical differences between very long-chain acyl-CoA dehydrogenase deficiency and long-chain acyl-CoA dehydrogenase deficiency in the mouse.

Journal Article (Journal Article)

Although many patients have been found to have very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency, none have been documented with long-chain acyl-CoA dehydrogenase (LCAD) deficiency. In order to understand the metabolic pathogenesis of long-chain fatty acid oxidation disorders, we generated mice with VLCAD deficiency (VLCAD(-/-)) and compared their pathologic and biochemical phenotypes of mice with LCAD deficiency (LCAD(-/-)) and wild-type mice. VLCAD(-/-) mice had milder fatty change in liver and heart. Dehydrogenation of various acyl-CoA substrates by liver, heart and skeletal muscle mitochondria differed among the three genotypes. The results for liver were most informative as VLCAD(-/-) mice had a reduction in activity toward palmitoyl-CoA and oleoyl-CoA (58 and 64% of wild-type, respectively), whereas LCAD(-/-) mice showed a more profoundly reduced activity toward these substrates (35 and 32% of wild-type, respectively), with a significant reduction of activity toward the branched chain substrate 2,6-dimethylheptanoyl-CoA. C(16) and C(18) acylcarnitines were elevated in bile, blood and serum of fasted VLCAD(-/-) mice, whereas abnormally elevated C(12) and C(14) acylcarnitines were prominent in LCAD(-/-) mice. Progeny with the combined LCAD(+/+)//VLCAD(+/-) genotype were over-represented in offspring from sires and dams heterozygous for both LCAD and VLCAD mutations. In contrast, no live mice with a compound LCAD(-/-)//VLCAD(-/-) genotype were detected.

Full Text

Duke Authors

Cited Authors

  • Cox, KB; Hamm, DA; Millington, DS; Matern, D; Vockley, J; Rinaldo, P; Pinkert, CA; Rhead, WJ; Lindsey, JR; Wood, PA

Published Date

  • September 15, 2001

Published In

Volume / Issue

  • 10 / 19

Start / End Page

  • 2069 - 2077

PubMed ID

  • 11590124

International Standard Serial Number (ISSN)

  • 0964-6906

Digital Object Identifier (DOI)

  • 10.1093/hmg/10.19.2069


  • eng

Conference Location

  • England