Zl. Lin et al., Genomic organization, expression, and alternate splicing of the mouse fatty aldehyde dehydrogenase gene, MOL GEN MET, 71(3), 2000, pp. 496-505
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 Sjogren-Larsson syndro
me (SLS) which is characterized by ichthyosis, mental retardation, and spas
ticity. To better understand SLS and the expression of FALDH in mammalian t
issues, we investigated the organization and expression of the mouse FALDH
gene (recently named ALDH3A2). The mouse gene consists of 11 exons and span
s about 25 kb. Primer extension experiments identified the transcription in
itiation site at nt -121 relative to the translation initiating codon. The
major FALDH transcript peas 3 kb long and was composed of exons 1-10. A les
s abundant alternately spliced transcript contained an additional exon (exo
n 9') inserted between exons 9 and 10 and encodes a protein (FALDHv) with a
variant carboxy-terminal domain of unknown function. Northern analysis usi
ng RNA 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 pr
ovide a basis for investigating the in Dire expression of FALDH in response
to physiologic and pharmacologic manipulation, and are essential for the d
evelopment of an animal model of SLS. (C) 2000 Academic Press.