Gene Symbol: Aldh1a2
Description: aldehyde dehydrogenase 1 family, member A2
Alias: Raldh-2, retinal dehydrogenase 2, RALDH 2, RalDH(II), aldehyde dehydrogenase 1A2, aldehyde dehydrogenase family 1 member A2, aldehyde dehydrogenase family 1, subfamily A2, ralDH2, retinal dehydrogenase, type II, retinaldehyde-specific dehydrogenase type 2
Species: rat
Products:     Aldh1a2

Top Publications

  1. Wang X, Penzes P, Napoli J. Cloning of a cDNA encoding an aldehyde dehydrogenase and its expression in Escherichia coli. Recognition of retinal as substrate. J Biol Chem. 1996;271:16288-93 pubmed
    ..These data support a function for RalDH(II) in the pathway of retinoic acid biogenesis. ..
  2. Napoli J. Physiological insights into all-trans-retinoic acid biosynthesis. Biochim Biophys Acta. 2012;1821:152-67 pubmed publisher physiological catalysts of the first step in atRA biosynthesis, and for the retinal dehydrogenases RALDH1, RALDH2, and RALDH3, as catalysts of the second and irreversible step...
  3. Okano J, Sakai Y, Shiota K. Retinoic acid down-regulates Tbx1 expression and induces abnormal differentiation of tongue muscles in fetal mice. Dev Dyn. 2008;237:3059-70 pubmed publisher
    ..Our study suggests that RA signaling may play an essential role in tongue muscle differentiation via the regulation of Tbx1. ..
  4. Deak K, Dickerson M, Linney E, Enterline D, George T, Melvin E, et al. Analysis of ALDH1A2, CYP26A1, CYP26B1, CRABP1, and CRABP2 in human neural tube defects suggests a possible association with alleles in ALDH1A2. Birth Defects Res A Clin Mol Teratol. 2005;73:868-75 pubmed
    ..We chose to investigate 5 genes involved in the metabolism or synthesis of RA, ALDH1A2, CYP26A1, CYP26B1, CRABP1, and CRABP2, for their role in the development of human neural tube defects, such as ..
  5. Niederreither K, Vermot J, Le Roux I, Schuhbaur B, Chambon P, Dolle P. The regional pattern of retinoic acid synthesis by RALDH2 is essential for the development of posterior pharyngeal arches and the enteric nervous system. Development. 2003;130:2525-34 pubmed
    Targeted inactivation of the mouse retinaldehyde dehydrogenase 2 (RALDH2/ALDH1a2), the enzyme responsible for early embryonic retinoic acid synthesis, is embryonic lethal because of defects in early heart morphogenesis...
  6. Mey J, Babiuk R, Clugston R, Zhang W, Greer J. Retinal dehydrogenase-2 is inhibited by compounds that induce congenital diaphragmatic hernias in rodents. Am J Pathol. 2003;162:673-9 pubmed
    ..Specifically, inhibition of retinal dehydrogenase-2 (RALDH2), a key enzyme necessary for the production of retinoic acid and that is expressed in the developing diaphragm, ..
  7. Vermot J, Niederreither K, Garnier J, Chambon P, Dolle P. Decreased embryonic retinoic acid synthesis results in a DiGeorge syndrome phenotype in newborn mice. Proc Natl Acad Sci U S A. 2003;100:1763-8 pubmed a decrease in embryonic RA levels, we generated mice bearing a hypomorphic allele of the RA-synthesizing enzyme Raldh2. The resulting mutant mice, which die perinatally, exhibit the features of the human DiGeorge syndrome (DGS) with ..
  8. Wang Z, Dolle P, Cardoso W, Niederreither K. Retinoic acid regulates morphogenesis and patterning of posterior foregut derivatives. Dev Biol. 2006;297:433-45 pubmed
    ..Here we show that mouse embryos deficient for the RA-synthesizing enzyme retinaldehyde dehydrogenase 2 (RALDH2), if rescued from early lethality by maternal RA supplementation between E7.5 and E8...
  9. Desai T, Chen F, LU J, Qian J, Niederreither K, Dolle P, et al. Distinct roles for retinoic acid receptors alpha and beta in early lung morphogenesis. Dev Biol. 2006;291:12-24 pubmed
    ..We analyzed initiation of lung development in retinaldehyde dehydrogenase-2 (Raldh2) null mice, a model in which RA signaling is absent from the foregut from its earliest developmental stages...

More Information


  1. Zhao X, Brade T, Cunningham T, Duester G. Retinoic acid controls expression of tissue remodeling genes Hmgn1 and Fgf18 at the digit-interdigit junction. Dev Dyn. 2010;239:665-71 pubmed publisher
    ..Here, we report that the RA-generating enzyme retinaldehyde dehydrogenase-2 (Raldh2) is expressed in the interdigital mesenchyme whereas Cyp26b1, controlling RA degradation, is expressed in digits, ..
  2. Moerman P, Goddeeris P, Lauwerijns J, van der Hauwaert L. Cardiovascular malformations in DiGeorge syndrome (congenital absence of hypoplasia of the thymus). Br Heart J. 1980;44:452-9 pubmed
  3. Spiegl N, Didichenko S, McCaffery P, Langen H, Dahinden C. Human basophils activated by mast cell-derived IL-3 express retinaldehyde dehydrogenase-II and produce the immunoregulatory mediator retinoic acid. Blood. 2008;112:3762-71 pubmed publisher
    ..Retinaldehyde dehydrogenase-II (RALDH2) creates localized RA gradients needed for proper embryonic development, but very little is known regarding its ..
  4. Martin M, Gallego Llamas J, Ribes V, Kedinger M, Niederreither K, Chambon P, et al. Dorsal pancreas agenesis in retinoic acid-deficient Raldh2 mutant mice. Dev Biol. 2005;284:399-411 pubmed
    ..development, we have studied the phenotype of mice with a targeted deletion in the retinaldehyde dehydrogenase 2 (Raldh2) gene, encoding the enzyme required to synthesize RA in the embryo...
  5. Ogura Y, Suruga K, Mochizuki H, Yamamoto T, Takase S, Goda T. Postnatal changes in gene expression of retinal dehydrogenase and retinoid receptors in liver of rats. Life Sci. 2004;74:1519-28 pubmed
    ..Northern blot analysis showed that RALDH2 mRNA levels decreased in the suckling period, whereas RALDH1 mRNA levels increased in the weaning period...
  6. Zhao D, McCaffery P, Ivins K, Neve R, Hogan P, Chin W, et al. Molecular identification of a major retinoic-acid-synthesizing enzyme, a retinaldehyde-specific dehydrogenase. Eur J Biochem. 1996;240:15-22 pubmed
  7. Zhuang R, Lin M, Napoli J. cis-Retinol/androgen dehydrogenase, isozyme 3 (CRAD3): a short-chain dehydrogenase active in a reconstituted path of 9-cis-retinoic acid biosynthesis in intact cells. Biochemistry. 2002;41:3477-83 pubmed
    ..intact cells, in conjunction with each of three retinal dehydrogenases that recognize 9-cis-retinal (RALDH1/AHD2, RALDH2, and ALDH12)...
  8. Wendling O, Chambon P, Mark M. Retinoid X receptors are essential for early mouse development and placentogenesis. Proc Natl Acad Sci U S A. 1999;96:547-51 pubmed
    ..Interestingly, as a RXR ligand appears dispensable, placentogenesis must be controlled by a yet unknown hormonal ligand(s) activating the heterodimerization partner(s) of RXRs. ..
  9. Ogura Y, Suruga K, Takase S, Goda T. Developmental changes of the expression of the genes regulated by retinoic acid in the small intestine of rats. Life Sci. 2005;77:2804-13 pubmed
    ..Northern blot analysis showed that both retinal dehydrogenase 1 (RALDH1) and retinal dehydrogenase 2 (RALDH2) mRNA levels were higher in 19-day fetal (2 days before birth) small intestine and then declined ..
  10. Chia I, Grote D, Marcotte M, Batourina E, Mendelsohn C, Bouchard M. Nephric duct insertion is a crucial step in urinary tract maturation that is regulated by a Gata3-Raldh2-Ret molecular network in mice. Development. 2011;138:2089-97 pubmed publisher
    ..We find a similar set of malformations in mutants lacking either Gata3 or Raldh2. We show that these factors act in parallel to regulate ND insertion via Ret...
  11. Li X, Kakkad B, Ong D. Estrogen directly induces expression of retinoic acid biosynthetic enzymes, compartmentalized between the epithelium and underlying stromal cells in rat uterus. Endocrinology. 2004;145:4756-62 pubmed
    ..eRolDH and RalDH II and their mRNAs were also increased in uteri of rats during estrus...
  12. Sirbu I, Gresh L, Barra J, Duester G. Shifting boundaries of retinoic acid activity control hindbrain segmental gene expression. Development. 2005;132:2611-22 pubmed
    Retinoic acid (RA) generated by Raldh2 in paraxial mesoderm is required for specification of the posterior hindbrain, including restriction of Hoxb1 expression to presumptive rhombomere 4 (r4)...
  13. Mic F, Duester G. Patterning of forelimb bud myogenic precursor cells requires retinoic acid signaling initiated by Raldh2. Dev Biol. 2003;264:191-201 pubmed
    ..Hgf expression in forelimb buds is dependent on retinoic acid (RA) synthesized by retinaldehyde dehydrogenase 2 (Raldh2) expressed proximally...
  14. Uehara M, Yashiro K, Mamiya S, Nishino J, Chambon P, Dolle P, et al. CYP26A1 and CYP26C1 cooperatively regulate anterior-posterior patterning of the developing brain and the production of migratory cranial neural crest cells in the mouse. Dev Biol. 2007;302:399-411 pubmed
  15. Molotkov A, Molotkova N, Duester G. Retinoic acid generated by Raldh2 in mesoderm is required for mouse dorsal endodermal pancreas development. Dev Dyn. 2005;232:950-7 pubmed
    ..We have analyzed mouse embryos carrying a null mutation of the gene encoding retinaldehyde dehydrogenase 2 (Raldh2), which controls RA synthesis...
  16. Everts H, Sundberg J, Ong D. Immunolocalization of retinoic acid biosynthesis systems in selected sites in rat. Exp Cell Res. 2005;308:309-19 pubmed
    ..uterus consisting of cellular retinol binding protein (Crbp), epithelial retinol dehydrogenase (eRoldh), retinal dehydrogenase 2 (Aldh1a2), and cellular retinoic acid binding protein type II (Crabp2)...
  17. Halilagic A, Ribes V, Ghyselinck N, Zile M, Dolle P, Studer M. Retinoids control anterior and dorsal properties in the developing forebrain. Dev Biol. 2007;303:362-75 pubmed
    We have previously shown that retinoic acid (RA) synthesized by the retinaldehyde dehydrogenase 2 (RALDH2) is required in forebrain development...
  18. Kim H, Lapointe J, Kaygusuz G, Ong D, Li C, van de Rijn M, et al. The retinoic acid synthesis gene ALDH1a2 is a candidate tumor suppressor in prostate cancer. Cancer Res. 2005;65:8118-24 pubmed
    ..prostate tissue, and the decreased expression of only one gene, aldehyde dehydrogenase 1 family, member A2 (ALDH1a2), was also associated with shorter recurrence-free survival...
  19. Zhai Y, Sperkova Z, Napoli J. Cellular expression of retinal dehydrogenase types 1 and 2: effects of vitamin A status on testis mRNA. J Cell Physiol. 2001;186:220-32 pubmed
    ..Liver expressed RALDH1 and RALDH2 only in stellate cells and hepatocytes, respectively...
  20. Lamb A, Newcomer M. The structure of retinal dehydrogenase type II at 2.7 A resolution: implications for retinal specificity. Biochemistry. 1999;38:6003-11 pubmed
    ..Retinal dehydrogenase type II (RalDH2) catalyzes this last step in the production of retinoic acid in the early embryo, possibly producing this putative ..
  21. Lai L, Bohnsack B, Niederreither K, Hirschi K. Retinoic acid regulates endothelial cell proliferation during vasculogenesis. Development. 2003;130:6465-74 pubmed
    ..We used mice rendered RA-deficient via targeted deletion of retinaldehyde dehydrogenase 2 (Raldh2(-/-)), the enzyme required to produce active RA in the embryo. Histological examination at E8.0-8...
  22. Maly I, Crotet V, Toranelli M. The so-called "testis-specific aldehyde dehydrogenase" corresponds to type 2 retinaldehyde dehydrogenase in the mouse. Histochem Cell Biol. 2003;119:169-74 pubmed
    ..The tissue distribution as well as substrate specificity and isoelectric points indicate that the "testis-specific aldehyde dehydrogenase" corresponds to mouse type 2 retinaldehyde dehydrogenase. ..
  23. Molotkova N, Molotkov A, Sirbu I, Duester G. Requirement of mesodermal retinoic acid generated by Raldh2 for posterior neural transformation. Mech Dev. 2005;122:145-55 pubmed
    ..We have tested this hypothesis in retinaldehyde dehydrogenase-2 (Raldh2) null mutant mice lacking RA synthesis in the somitic mesoderm...
  24. Fujiwara K, Maekawa F, Kikuchi M, Takigami S, Yada T, Yashiro T. Expression of retinaldehyde dehydrogenase (RALDH)2 and RALDH3 but not RALDH1 in the developing anterior pituitary glands of rats. Cell Tissue Res. 2007;328:129-35 pubmed
    ..In this study, we examined the expression of RALDH1, RALDH2, and RALDH3 mRNA in the rat embryonic pituitary gland...
  25. Marlier A, Gilbert T. Expression of retinoic acid-synthesizing and -metabolizing enzymes during nephrogenesis in the rat. Gene Expr Patterns. 2004;5:179-85 pubmed
    ..b>ALDH1A2 expression was restricted to the cortical stroma cell population, whereas ALDH8A1 transcripts were present in ..
  26. Vermot J, Schuhbaur B, Le Mouellic H, McCaffery P, Garnier J, Hentsch D, et al. Retinaldehyde dehydrogenase 2 and Hoxc8 are required in the murine brachial spinal cord for the specification of Lim1+ motoneurons and the correct distribution of Islet1+ motoneurons. Development. 2005;132:1611-21 pubmed
    ..using a conditional knockout strategy that ablates the function of the retinaldehyde dehydrogenase 2 (Raldh2) synthesizing enzyme essentially in brachial motoneurons, and later in mesenchymal cells at the base of the ..
  27. Vermot J, Gallego Llamas J, Fraulob V, Niederreither K, Chambon P, Dolle P. Retinoic acid controls the bilateral symmetry of somite formation in the mouse embryo. Science. 2005;308:563-6 pubmed
    ..These data implicate retinoic acid as an endogenous signal that maintains the bilateral synchrony of mesoderm segmentation, and therefore controls bilateral symmetry, in vertebrate embryos. ..
  28. Mic F, Sirbu I, Duester G. Retinoic acid synthesis controlled by Raldh2 is required early for limb bud initiation and then later as a proximodistal signal during apical ectodermal ridge formation. J Biol Chem. 2004;279:26698-706 pubmed
    ..Limb RA synthesis is under the control of retinaldehyde dehydrogenase-2 (Raldh2) expressed in the lateral plate mesoderm, which generates a proximodistal RA signal during limb outgrowth...
  29. Mic F, Molotkov A, Molotkova N, Duester G. Raldh2 expression in optic vesicle generates a retinoic acid signal needed for invagination of retina during optic cup formation. Dev Dyn. 2004;231:270-7 pubmed
    Three retinaldehyde dehydrogenase genes (Raldh1, Raldh2, and Raldh3) expressed in unique spatiotemporal patterns may control synthesis of retinoic acid (RA) needed for retina development...
  30. Wang C, KANE M, Napoli J. Multiple retinol and retinal dehydrogenases catalyze all-trans-retinoic acid biosynthesis in astrocytes. J Biol Chem. 2011;286:6542-53 pubmed publisher
    ..Immunocytochemistry revealed cytosolic and nuclear expression of Raldh1 and cytosol and perinuclear expression of Raldh2. atRA autoregulated its concentrations by inducing retinyl ester synthesis via lecithin:retinol acyltransferase ..
  31. Niederreither K, Vermot J, Messaddeq N, Schuhbaur B, Chambon P, Dolle P. Embryonic retinoic acid synthesis is essential for heart morphogenesis in the mouse. Development. 2001;128:1019-31 pubmed
    ..To block endogenous RA synthesis, we have disrupted the gene encoding RALDH2, the first retinaldehyde dehydrogenase whose expression has been detected during early mouse post-implantation ..