Analysis of the expression of murine glutaryl-CoA dehydrogenase: In vitro and in vivo Studies

Glutaric acidemia type I (GAI) is an autosomal recessive organic acidemia c aused by a mutation in the gene encoding glutaryl-CoA dehydrogenase (GCD). Clinically, GAI is characterized by progressive dystonia, resulting from de generation 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 vitro approaches. Transfection studies mapped the mouse GCD promote r 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 se veral transcription factors with roles in the regulation of nuclear genes e ncoding mitochondrial proteins. Western blot and RT/PCR analyses of mouse t issues demonstrated that GCD is ubiquitously expressed, with the highest le vels of expression in liver and kidney, consistent with its role in amino a cid oxidation. Expression in multiple regions of the brain was also detecte d by Western blotting. Based on these results we conclude that the specific neuropathology associated with GCD deficiency in GAI cannot be accounted f or by its expression pattern. (C) 2000 Academic Press.