PMID- 10191271
OWN - NLM
STAT- MEDLINE
DCOM- 19990623
LR  - 20181113
IS  - 0264-6021 (Print)
IS  - 0264-6021 (Linking)
VI  - 339 ( Pt 2)
DP  - 1999 Apr 15
TI  - Molecular analysis of two closely related mouse aldehyde dehydrogenase genes:
      identification of a role for Aldh1, but not Aldh-pb, in the biosynthesis of
      retinoic acid.
PG  - 387-95
AB  - Mammalian class I aldehyde dehydrogenase (ALDH1) has been implicated as a retinal
      dehydrogenase in the biosynthesis of retinoic acid, a modulator of gene
      expression and cell differentiation. As the first step towards studying the
      regulation of ALDH1 and its physiological role in the biosynthesis of retinoic
      acid, mouse ALDH1 cDNA and genomic clones have been characterized. During the
      cloning process, an additional closely related gene was also isolated and named
      Aldh-pb, owing to its high amino acid sequence identity (92%) with the rat
      phenobarbitol-inducible ALDH protein (ALDH-PB). Aldh1 spans about 45 kb in
      length, whereas Aldh-pb spans about 35 kb. Both genes are composed of 13 exons,
      and the positions of all the exon/intron boundaries are conserved with those of
      human ALDH1. The promoter regions of Aldh1 and Aldh-pb demonstrate high sequence 
      similarity with those of human ALDH1 and rat ALDH-PB. Expression of Aldh1 and
      Aldh-pb is tissue-specific, with mRNAs for both genes being found in the liver,
      lung and testis, but not in the heart, spleen or muscle. Expression of Aldh-pb,
      but not Aldh1, was also detected at high levels in the kidney. Aldh1 and Aldh-pb 
      encode proteins of 501 amino acids with 90% positional identity. To examine the
      relative roles of these two enzymes in retinoic acid synthesis in vivo, Xenopus
      embryos were injected with mRNAs encoding these enzymes to assay the effect on
      conversion of endogenous retinal into retinoic acid. Injection of ALDH1, but not 
      ALDH-PB, mRNA stimulated retinoic acid synthesis in Xenopus embryos at the
      blastula stage. Thus our results indicate that Aldh1 can function in retinoic
      acid synthesis under physiological conditions, but that the closely related
      Aldh-pb does not share this property.
FAU - Hsu, L C
AU  - Hsu LC
AD  - Department of Biochemical Genetics, Beckman Research Institute of the City of
      Hope, Duarte, CA 91010, USA.
FAU - Chang, W C
AU  - Chang WC
FAU - Hoffmann, I
AU  - Hoffmann I
FAU - Duester, G
AU  - Duester G
LA  - eng
GR  - AA09731/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (DNA, Complementary)
RN  - 0 (Isoenzymes)
RN  - 5688UTC01R (Tretinoin)
RN  - EC 1.2.1.3 (Aldehyde Dehydrogenase)
SB  - IM
MH  - Aldehyde Dehydrogenase/*genetics
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - Cloning, Molecular
MH  - DNA, Complementary
MH  - Exons
MH  - Humans
MH  - Introns
MH  - Isoenzymes/*genetics
MH  - Mice
MH  - Molecular Sequence Data
MH  - Sequence Homology, Amino Acid
MH  - Sequence Homology, Nucleic Acid
MH  - Tretinoin/*metabolism
PMC - PMC1220169
EDAT- 1999/04/07 00:00
MHDA- 1999/04/07 00:01
CRDT- 1999/04/07 00:00
PHST- 1999/04/07 00:00 [pubmed]
PHST- 1999/04/07 00:01 [medline]
PHST- 1999/04/07 00:00 [entrez]
PST - ppublish
SO  - Biochem J. 1999 Apr 15;339 ( Pt 2):387-95.