Fatty aldehyde dehydrogenase (FALDH) is a microsomal enzyme that catalyzes the oxidation of aliphatic aldehydes to fatty acids. Mutations in the FALDH gene are responsible for the human genetic disorder Sjögren-Larsson syndrome (SLS) which is characterized by ichthyosis, mental retardation, and spasticity. To better understand SLS and the expression of FALDH in mammalian tissues, we investigated the organization and expression of the mouse FALDH gene (recently named ALDH3A2). The mouse gene consists of 11 exons and spans about 25 kb. Primer extension experiments identified the transcription initiation site at nt -121 relative to the translation initiating codon. The major FALDH transcript was 3 kb long and was composed of exons 1-10. A less abundant alternately spliced transcript contained an additional exon (exon 9') inserted between exons 9 and 10 and encodes a protein (FALDHv) with a variant carboxy-terminal domain of unknown function. Northern analysis usingRNA from different tissues showed widespread but variable expression of the gene, which generally correlated with FALDH enzyme activity. Expression of the alternate exon 9' transcript in tissues often differed from that of the major transcript and did not reflect enzyme activity. These results provide a basis for investigating the in vivo expression of FALDH in response to physiologic and pharmacologic manipulation, and are essential for the development of an animal model of SLS.
Copyright 2000 Academic Press.