title: Analysis of the expression of murine glutaryl-CoA dehydrogenase: in vitro and in vivo studies.
abstract: Glutaric acidemia type I (GAI) is an autosomal recessive organic acidemia caused by a mutation in the gene encoding glutaryl-CoA dehydrogenase (GCD). Clinically, GAI is characterized by progressive dystonia, resulting from degeneration of neurons in the caudate and putamen nuclei of the striatum. In an attempt to understand the basis for the specific neuropathology in GAI, we have analyzed the expression of the murine GCD gene using both in vitro and in vivo approaches. Transfection studies mapped the mouse GCD promoter to a 500-bp region of DNA 5' of the translation start site. The promoter lacks a TATA consensus sequence, but includes possible binding sites for several transcription factors with roles in the regulation of nuclear genes encoding mitochondrial proteins. Western blot and RT/PCR analyses of mouse tissues demonstrated that GCD is ubiquitously expressed, with the highest levels of expression in liver and kidney, consistent with its role in amino acid oxidation. Expression in multiple regions of the brain was also detected by Western blotting. Based on these results we conclude that the specific neuropathology associated with GCD deficiency in GAI cannot be accounted for by its expression pattern.
authors.affiliation: Department of Pediatrics, University of Colorado Health Sciences Center, Denver, Colorado, 80262, USA.
authors.forename: M
authors.initials: M
authors.lastname: Woontner
authors.forename: L S
authors.initials: LS
authors.lastname: Crnic
authors.forename: D M
authors.initials: DM
authors.lastname: Koeller
mesh_terms: D016475:3T3 Cells; D020121:5' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D005977:Glutarates / Q000494:pharmacology; D050770:Glutaryl-CoA Dehydrogenase; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008239:Lysine / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010088:Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D044925:Oxidoreductases Acting on CH-CH Group Donors; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D014162:Transfection
chemical_list: D020121:5' Untranslated Regions; D005977:Glutarates; D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors; D050770:Glutaryl-CoA Dehydrogenase; C035736:glutaric acid; D008239:Lysine