Previously we have shown that all SELH/Bc mouse embryos close their anterior neural tubes by an abnormal mechanism and that 10-20% of SELH/Bc embryos are exencephalic. The purposes of these studies were (1) to observe the effects of
retinoic acid on the frequency of
exencephaly in SELH/Bc embryos; (2) to compare the SELH/Bc response with those of normal strains and of other neural tube mutants; and (3) to compare, between SELH/Bc and a normal strain (SWV/Bc), the effects of
retinoic acid on morphology of the closing anterior neural tube. SELH/Bc was more liable to
retinoic acid-induced
exencephaly than were normal strains. After maternal treatment with 5 mg/kg
retinoic acid on day 8.5 of gestation, 53% of SELH/Bc embryos had
exencephaly, compared with 22% in ICR/Bc and 14% in SWV/Bc. When these results were transformed according to the assumptions of the developmental threshold model, the effects of genotype and
retinoic acid appeared to be additive. Similar treatment on day 9 or 10 of gestation had little or no effect on the frequency of
exencephaly in SELH/Bc mice. These results are similar to the reported responses of the curly-tail and Splotch mutants, where frequencies of
spina bifida but not
exencephaly were decreased. This pattern suggests that studies of effects of periconceptional
vitamin treatment on risk of human
neural tube defects should consider
anencephaly and
spina bifida separately. The study comparing the morphology of anterior neural tube closure in SELH/Bc and normal SWV/Bc embryos showed that
retinoic acid delays the elevation of the mesencephalic neural folds. This results in a "stalling" of many embryos in the first steps of neural tube closure, with their neural folds remaining convex and splayed wide apart. The delay in fold elevation was superimposed on the different closure patterns of the two strains. The overall conclusion is that there is no nonadditive interaction in the parameters studied between
retinoic acid treatment and the SELH/Bc genotype.