title: Interaction between the splotch mutation and retinoic acid in mouse neural tube defects in vitro.
abstract: The interaction between the splotch gene (Sp) and all-trans retinoic acid (RA) was investigated using cytogenetically marked Sp/+ and +/+ mouse embryos cultured in the presence of RA. Retinoic acid retarded the development of and had a teratogenic effect on mouse embryos in culture. In particular, RA had seemingly opposite effects on the posterior neural tube, inducing abnormally early fusion in some embryos and causing a dose-dependent delay in others. When the effects of RA on identified Sp/+ and +/+ embryos were compared, the only observed difference in their responses was in the degree of the delay in posterior neuropore (PNP) closure. At the end of the culture period, among the untreated control embryos, the Sp heterozygotes showed retardation of PNP closure compared to +/+ embryos. In addition, the RA treatment was found to have induced a greater delay in posterior neural tube closure in Sp/+ than in +/+ embryos. The basis for this difference in response to RA is presumed to be the retardation of PNP closure that is caused by the Sp gene in heterozygous form. The effects of the gene and the teratogen are additive and the gene carriers thus have greater mean PNP lengths at the end of culture. Since the length of the PNP is an indication of an embryo's likelihood of developing spina bifida, this provides an explanation for the observation that Sp/+ embryos are more sensitive to the spina bifida-causing effects of RA than are +/+ embryos.
authors.affiliation: Department of Biology, McGill University, Montreal, Quebec, Canada.
authors.forename: C M
authors.initials: CM
authors.lastname: Kapron-Brás
authors.forename: D G
authors.initials: DG
authors.lastname: Trasler
mesh_terms: D000818:Animals; D046508:Culture Techniques; D051379:Mice; D008818:Mice, Neurologic Mutants; D009154:Mutation; D009436:Neural Tube Defects / Q000235:genetics*; D013723:Teratogens; D014212:Tretinoin / Q000633:toxicity*
chemical_list: D013723:Teratogens; D014212:Tretinoin