A newborn lethal defect due to inactivation of retinaldehyde dehydrogenase type 3 is prevented by maternal retinoic acid treatment.
The retinoic acid (RA) signal, produced locally from vitamin A by retinaldehyde dehydrogenase (Raldh) and transduced by the nuclear receptors for retinoids (RA receptor and 9-cis-RA receptor), is indispensable for ontogenesis and homeostasis of numerous tissues. We demonstrate that Raldh3 knockout in mouse suppresses RA synthesis and causes malformations restricted to ocular and nasal regions, which are similar to those observed in vitamin A-deficient fetuses and/or in retinoid receptor mutants. Raldh3 knockout notably causes choanal atresia (CA), which is responsible for respiratory distress and death of Raldh3-null mutants at birth. CA is due to persistence of nasal fins, whose rupture normally allows the communication between nasal and oral cavities. This malformation, which is similar to isolated congenital CA in humans and may result from impaired RA-controlled down-regulation of Fgf8 expression in nasal fins, can be prevented by a simple maternal treatment with RA.
Dupé
Valérie
V
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Université Louis Pasteur, Collège de France, BP10142, 67404 Illkirch Cedex, Communauté Urbaine de Strasbourg, France.
Matt
Nicolas
N
Garnier
Jean-Marie
JM
Chambon
Pierre
P
Mark
Manuel
M
Ghyselinck
Norbert B
NB
D000445:Aldehyde Oxidoreductases / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D002754:Choanal Atresia / Q000196:embryology / Q000235:genetics / Q000517:prevention & control; D004247:DNA / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D018390:Gene Targeting; D005804:Genes, Lethal; D006801:Humans; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D008431:Maternal-Fetal Exchange; D051379:Mice; D018345:Mice, Knockout; D011247:Pregnancy; D050697:Retinal Dehydrogenase; D014212:Tretinoin / Q000494:pharmacology*
D007527:Isoenzymes; D014212:Tretinoin; D004247:DNA; D000445:Aldehyde Oxidoreductases; D050697:Retinal Dehydrogenase