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Gene Review

Aldh1a2  -  aldehyde dehydrogenase family 1, subfamily A2

Mus musculus

Synonyms: AV116159, Aldehyde dehydrogenase family 1 member A2, Aldh1a7, RALDH 2, RALDH(II), ...
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Disease relevance of Aldh1a2


High impact information on Aldh1a2

  • Here we show that production of RA by the retinaldehyde dehydrogenase-2 (Raldh2) enzyme is required for mouse embryo survival and early morphogenesis [6].
  • Raldh2 is an NAD-dependent aldehyde dehydrogenase with high substrate specificity for retinaldehyde [6].
  • We generated a targeted disruption of the mouse Raldh2 gene and found that Raldh2-/- embryos, which die at midgestation without undergoing axial rotation (body turning), exhibit shortening along the anterioposterior axis and do not form limb buds [6].
  • Exogenous provision of RA or Fn to Raldh2(-/-) explants in whole mouse embryo culture restored vascular remodeling, visceral endoderm survival, as well as integrin alpha5 expression and its downstream signaling that controls endothelial growth [7].
  • We found that although the enzyme required for RA production during early embryogenesis, retinaldehyde dehydrogenase-2 (Raldh2), was expressed in the visceral endoderm, RA receptors alpha1 and alpha2 were expressed in endothelial cells in the mesoderm, indicating that they are direct targets of RA [7].

Chemical compound and disease context of Aldh1a2


Biological context of Aldh1a2


Anatomical context of Aldh1a2

  • However, reporter transgene activity was selectively detected in Raldh2(-/-) embryos within the mesonephric area that expresses RALDH3 and in medial-ventral cells of the spinal cord and posterior hindbrain, up to the level of the fifth rhombomere [10].
  • These data suggest the existence of additional RA-generating activities in the differentiating forebrain, hindbrain, and spinal cord, which, along with RALDH1 and RALDH3, may account for the development of Raldh2(-/-) mutants once these have been rescued for early lethality [10].
  • Although these patterns correlated with the presence of Raldh1 andor Raldh3 transcripts in eye, nasal, and inner ear epithelia, no such correlation was found within forebrain neuroepithelium [10].
  • Retrograde labeling of adult Raldh1(-/-) retinal ganglion cells indicated that dorsal retinal axons project to the superior colliculus, and electroretinography revealed no defect of adult visual function, suggesting that dorsal RA signaling is unnecessary for retinal ganglion cell axonal outgrowth [13].
  • RA signaling in the optic cup, detected by using a RARE-lacZ transgene, is not significantly altered in Raldh1(-/-) embryos at embryonic day 10.5, possibly due to normal expression of Aldh1a3 (Raldh3) in dorsal retinal pigment epithelium and ventral neural retina [13].

Associations of Aldh1a2 with chemical compounds

  • Hair cycle-specific immunolocalization of retinoic acid synthesizing enzymes Aldh1a2 and Aldh1a3 indicate complex regulation [14].
  • Expression of the RA synthesizing enzyme Raldh2 was also up-regulated and altered Hoxb1 expression indicated that RA levels are raised in R115866-treated embryos as reported for Tbx1 null mice [15].
  • One enzyme, located in the dorsal retina (corresponding to mouse RALDH-1), and one enzyme in the RPE (RALDH-2) were aldehyde dehydrogenases of the same molecular weight (monomers about 55 kDa) but with different isoelectric points (6.5-6.9; 4.9-5.4) [16].
  • We have identified the gene for the retinoic acid (RA) synthesis enzyme Aldh1a2 as a principal target of BMP signaling; prochondrogenic BMPs or GDFs lead to attenuation of Aldh1a2 expression and, consequently, to reduced activation of the retinoid signaling pathway [17].
  • Using genetic approaches in the mouse, we show that the primary target tissue of retinoic acid (RA) action during eye morphogenesis is not the retina nor the corneal ectoderm, which both express RA-synthesizing retinaldehyde dehydrogenases (RALDH1 and RALDH3), but the neural crest cell-derived periocular mesenchyme (POM), which is devoid of RALDH [18].

Regulatory relationships of Aldh1a2


Other interactions of Aldh1a2


Analytical, diagnostic and therapeutic context of Aldh1a2


  1. Restricted expression and retinoic acid-induced downregulation of the retinaldehyde dehydrogenase type 2 (RALDH-2) gene during mouse development. Niederreither, K., McCaffery, P., Dräger, U.C., Chambon, P., Dollé, P. Mech. Dev. (1997) [Pubmed]
  2. Embryonic retinoic acid synthesis is essential for heart morphogenesis in the mouse. Niederreither, K., Vermot, J., Messaddeq, N., Schuhbaur, B., Chambon, P., Dollé, P. Development (2001) [Pubmed]
  3. Molecular identification of a major retinoic-acid-synthesizing enzyme, a retinaldehyde-specific dehydrogenase. Zhao, D., McCaffery, P., Ivins, K.J., Neve, R.L., Hogan, P., Chin, W.W., Dräger, U.C. Eur. J. Biochem. (1996) [Pubmed]
  4. Levels of retinoic acid and retinaldehyde dehydrogenase expression in eyes of the Mitf-vit mouse model of retinal degeneration. Duncan, T., Swint, C., Smith, S.B., Wiggert, B.N. Mol. Vis. (1999) [Pubmed]
  5. Mouse type-2 retinaldehyde dehydrogenase (RALDH2): genomic organization, tissue-dependent expression, chromosome assignment and comparison to other types. Hsu, L.C., Chang, W.C., Yoshida, A. Biochim. Biophys. Acta (2000) [Pubmed]
  6. Embryonic retinoic acid synthesis is essential for early mouse post-implantation development. Niederreither, K., Subbarayan, V., Dollé, P., Chambon, P. Nat. Genet. (1999) [Pubmed]
  7. Signaling hierarchy downstream of retinoic acid that independently regulates vascular remodeling and endothelial cell proliferation. Bohnsack, B.L., Lai, L., Dolle, P., Hirschi, K.K. Genes Dev. (2004) [Pubmed]
  8. Genetic evidence that retinaldehyde dehydrogenase Raldh1 (Aldh1a1) functions downstream of alcohol dehydrogenase Adh1 in metabolism of retinol to retinoic acid. Molotkov, A., Duester, G. J. Biol. Chem. (2003) [Pubmed]
  9. Embryonic retinoic acid synthesis is required for forelimb growth and anteroposterior patterning in the mouse. Niederreither, K., Vermot, J., Schuhbaur, B., Chambon, P., Dollé, P. Development (2002) [Pubmed]
  10. Retinaldehyde dehydrogenase 2 (RALDH2)- independent patterns of retinoic acid synthesis in the mouse embryo. Niederreither, K., Vermot, J., Fraulob, V., Chambon, P., Dolle, P. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  11. Differential expression of retinoic acid-synthesizing (RALDH) enzymes during fetal development and organ differentiation in the mouse. Niederreither, K., Fraulob, V., Garnier, J.M., Chambon, P., Dollé, P. Mech. Dev. (2002) [Pubmed]
  12. A newborn lethal defect due to inactivation of retinaldehyde dehydrogenase type 3 is prevented by maternal retinoic acid treatment. Dupé, V., Matt, N., Garnier, J.M., Chambon, P., Mark, M., Ghyselinck, N.B. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  13. Targeted disruption of Aldh1a1 (Raldh1) provides evidence for a complex mechanism of retinoic acid synthesis in the developing retina. Fan, X., Molotkov, A., Manabe, S., Donmoyer, C.M., Deltour, L., Foglio, M.H., Cuenca, A.E., Blaner, W.S., Lipton, S.A., Duester, G. Mol. Cell. Biol. (2003) [Pubmed]
  14. Hair cycle-specific immunolocalization of retinoic acid synthesizing enzymes Aldh1a2 and Aldh1a3 indicate complex regulation. Everts, H.B., King, L.E., Sundberg, J.P., Ong, D.E. J. Invest. Dermatol. (2004) [Pubmed]
  15. Cyp26 genes a1, b1 and c1 are down-regulated in Tbx1 null mice and inhibition of Cyp26 enzyme function produces a phenocopy of DiGeorge Syndrome in the chick. Roberts, C., Ivins, S., Cook, A.C., Baldini, A., Scambler, P.J. Hum. Mol. Genet. (2006) [Pubmed]
  16. Sources and sink of retinoic acid in the embryonic chick retina: distribution of aldehyde dehydrogenase activities, CRABP-I, and sites of retinoic acid inactivation. Mey, J., McCaffery, P., Klemeit, M. Brain Res. Dev. Brain Res. (2001) [Pubmed]
  17. BMP action in skeletogenesis involves attenuation of retinoid signaling. Hoffman, L.M., Garcha, K., Karamboulas, K., Cowan, M.F., Drysdale, L.M., Horton, W.A., Underhill, T.M. J. Cell Biol. (2006) [Pubmed]
  18. Retinoic acid-dependent eye morphogenesis is orchestrated by neural crest cells. Matt, N., Dupé, V., Garnier, J.M., Dennefeld, C., Chambon, P., Mark, M., Ghyselinck, N.B. Development (2005) [Pubmed]
  19. Dorsal pancreas agenesis in retinoic acid-deficient Raldh2 mutant mice. Martín, M., Gallego-Llamas, J., Ribes, V., Kedinger, M., Niederreither, K., Chambon, P., Dollé, P., Gradwohl, G. Dev. Biol. (2005) [Pubmed]
  20. Dynamic expression of retinoic acid-synthesizing and -metabolizing enzymes in the developing mouse inner ear. Romand, R., Kondo, T., Fraulob, V., Petkovich, M., Dollé, P., Hashino, E. J. Comp. Neurol. (2006) [Pubmed]
  21. RALDH3, a retinaldehyde dehydrogenase that generates retinoic acid, is expressed in the ventral retina, otic vesicle and olfactory pit during mouse development. Mic, F.A., Molotkov, A., Fan, X., Cuenca, A.E., Duester, G. Mech. Dev. (2000) [Pubmed]
  22. Shifting boundaries of retinoic acid activity control hindbrain segmental gene expression. Sirbu, I.O., Gresh, L., Barra, J., Duester, G. Development (2005) [Pubmed]
  23. Retinoic acid generated by Raldh2 in mesoderm is required for mouse dorsal endodermal pancreas development. Molotkov, A., Molotkova, N., Duester, G. Dev. Dyn. (2005) [Pubmed]
  24. Complementary domains of retinoic acid production and degradation in the early chick embryo. Swindell, E.C., Thaller, C., Sockanathan, S., Petkovich, M., Jessell, T.M., Eichele, G. Dev. Biol. (1999) [Pubmed]
  25. Hot spots of retinoic acid synthesis in the developing spinal cord. McCaffery, P., Dräger, U.C. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  26. Retinoid signaling and cardiac anteroposterior segmentation. Xavier-Neto, J., Rosenthal, N., Silva, F.A., Matos, T.G., Hochgreb, T., Linhares, V.L. Genesis (2001) [Pubmed]
  27. Pharmacology of RALGA, a mixture of retinaldehyde and glycolic acid. Tran, C., Kasraee, B., Grand, D., Carraux, P., Didierjean, L., Sorg, O., Saurat, J.H. Dermatology (Basel) (2005) [Pubmed]
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