Conditional (loxP-flanked) allele for the gene encoding the retinoic acid-synthesizing enzyme retinaldehyde dehydrogenase 2 (RALDH2).
Retinoic acid, the active vitamin A derivative, has pleiotropic functions during vertebrate development and postnatal life. Retinaldehyde dehydrogenase 2 (RALDH2) acts as the main retinoic acid-synthesizing enzyme during development. Mouse Raldh2 germline null mutants are early embryonic lethal and exhibit complex abnormalities that include defective heart looping morphogenesis. To investigate later functions of this enzyme, we have engineered a "floxed" (loxP-flanked) allele allowing Cre-mediated somatic gene inactivations. Mice heterozygous or homozygous for the floxed Raldh2 allele are viable and fertile. We tested whether the novel Raldh2 allele behaves as a null mutation after Cre-mediated in vivo excision by crossing the conditional mutants with CMV-Cre transgenic mice. An embryonic lethal phenotype indistinguishable from that of germline mutants was obtained. The conditional allele described herein is a genetic tool for studying tissue-specific, RALDH2-dependent functions of retinoic acid during development and in adult life.
Vermot
Julien
J
Institut de Génétique et de Biologie Moléculaire et Cellulaire, UMR 7104 du CNRS, U. 596 de l'INSERM, Université Louis Pasteur, CU de Strasbourg, France.
Garnier
Jean-Marie
JM
Dierich
Andrée
A
Niederreither
Karen
K
Harvey
Richard P
RP
Chambon
Pierre
P
Dollé
Pascal
P
D000445:Aldehyde Oxidoreductases / Q000235:genetics*; D000483:Alleles; D000818:Animals; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology / Q000201:enzymology; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology; D018390:Gene Targeting; D005838:Genotype; D019426:Integrases / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic; D017384:Sequence Deletion; D014162:Transfection; D014212:Tretinoin / Q000378:metabolism*
D014212:Tretinoin; D000445:Aldehyde Oxidoreductases; C470579:RALDH2 protein, mouse; C045073:Cre recombinase; D019426:Integrases