Rj. Tolwani et al., STRUCTURE AND CHROMOSOMAL LOCATION OF THE MOUSE MEDIUM-CHAIN ACYL-COADEHYDROGENASE-ENCODING GENE AND ITS PROMOTER, Gene, 170(2), 1996, pp. 165-171
Medium-chain acyl-coenzyme A dehydrogenase (MCAD; mouse gene Acadm; hu
man gene ACADM) catalyzes the initial step of fatty acid beta-oxidatio
n in mitochondria. Inherited MCAD deficiency is an autosomal recessive
disorder that occurs at high frequency in humans and is associated wi
th considerable morbidity and mortality. We have cloned and characteri
zed mouse Acadm which spans approximately 25 kb and contains 12 exons.
The promoter region does not contain TATA or CAAT boxes and is G+C-ri
ch (60%) within 200 bp of the cap site. A CpG island extends from 5' o
f the transcription start point into intron 1. The 5' regulatory regio
n and a portion of intron 1 contain several Sp1 consensus sites and th
ree regions containing hexamer DNA sequences that match the binding co
nsensus for steroid/thyroid nuclear receptors. These putative nuclear
receptor response elements (NRRE) share DNA sequence homology and elec
trophoretic mobility shift characteristics with known NRRE in the huma
n ACADM promoter [Carter et al., J. Biol. Chem. 268 (1993) 13805-13810
]. We have mapped mouse Acadm to the distal end of chromosome 3. Seque
nces previously localized to chromosome 8 are shown to be a pseudogene
, and an additional pseudogene was identified on chromosome 11.