The identification of a 9-cis retinol dehydrogenase in the mouse embryo reveals a pathway for synthesis of 9-cis retinoic acid

The identification of a 9-cis retinol dehydrogenase in the mouse embryo reveals a pathway for synthesis of 9-cis retinoic acid

^*Ludwig Institute for Cancer Research, Stockholm Branch, Box 240, S-171 77 Stockholm, Sweden; and ^†Department of Pharmaceutical Biosciences, Division of Toxicology, Biomedical Centre, University of Uppsala, Box 594, S-751 24 Uppsala, Sweden

Edited by Pierre Chambon, Collège de France, Strasbourg, France, and approved January 16, 1998 (received for review September 30, 1997)

Abstract

The ligand-controlled retinoic acid (RA) receptors and retinoid X receptors are important for several physiological processes, including normal embryonic development, but little is known about how their ligands, all-trans and 9-cis RA, are generated. Here we report the identification of a stereo-specific 9-cis retinol dehydrogenase, which is abundantly expressed in embryonic tissues known to be targets in the retinoid signaling pathway. The membrane-bound enzyme is a member of the short-chain alcohol dehydrogenase/reductase superfamily, able to oxidize 9-cis retinol into 9-cis retinaldehyde, an intermediate in 9-cis RA biosynthesis. Analysis by nonradioactive in situ hybridization in mouse embryos shows that expression of the enzyme is temporally and spatially well controlled during embryogenesis with prominent expression in parts of the developing central nervous system, sensory organs, somites and myotomes, and several tissues of endodermal origin. The identification of this enzyme reveals a pathway in RA biosynthesis, where 9-cis retinol is generated for subsequent oxidation to 9-cis RA.

Footnotes

↵ ‡ To whom reprint requests should be addressed. e-mail: ueri{at}licr.ki.se.
This paper was submitted directly (Track II) to the Proceedings Office.
Abbreviations: gd, gestation day; RA, retinoic acid; RAR, retinoic acid receptor; RXR, retinoid X receptor; RDH, retinol dehydrogenase; SDR, short chain alcohol dehydrogenase/reductase; RT, reverse transcriptase.
Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession no. AF013288).