Neural tube defects in curly-tail mice. II. Effect of maternal administration of vitamin A

Abstract

Vitamin A, a known teratogen of the central nervous system, was administered in various doses, at the time of active neural tube closure, to pregnant curly-tail mice which have a genetic predisposition to neural tube defects (n. t. d. ), and to A Strong mice, which are not so predisposed. The curly-tail mice showed an enhanced susceptibility to the terato­genic effect of vitamin A given on day 8 of gestation, demonstrating a clear gene─environment interaction. There was a differential response by the two sexes. Females seemed to be more affected by the vitamin A than males. When vitamin A was administered on day 9, instead of day 8, of gestation, the incidence of n. t. d. decreased rather than increased. Furthermore, the number of mice affected by n. t. d. was markedly lower even than that found spontaneously in untreated curly-tail mice.

Role of differential cell proliferation in the tail bud in aberrant mouse neurulation

“…Moreover, the expression of the retinoid acid receptors RAR-␤ and RAR-␥ has also been found to be reduced in the curly tail embryo (Chen et al, 1995). Upregulation of RAR-␤ either by RA or inositol administration results in a normalization of PNP closure and a reduction of the incidence of spinal NTD in curly tail mice (Seller et al, 1979;Chen et al, 1994Chen et al, , 1995Greene and Copp, 1997). This indicates that RAR-␤, RAR-␥, and Wnt-5a are among the genes likely involved in the pathogenesis of the curly tail.…”

Insights into prevention of human neural tube defects by folic acid arising from consideration of mouse mutants

“…The curly tail strain, one of the few NTD models known in 1980, was tested extensively by Mary Seller (a coauthor of the clinical intervention study ;Smithells, et al, 1980). Of the vitamins tested in curly tail mice, only vitamin A given specifically on day 9 of gestation (GD 9) reduced the NTD frequency (Seller et al, 1979;Seller and Adinolfi, 1981). Folic acid or folinic acid given on GD 7 and GD 8 caused no reduction in NTD frequency in curly tail mice (Seller and Adinolfi, 1981).…”

legless insertional mutation: morphological, molecular, and genetic characterization.

“…Retinoic acid (RA) has been shown to alter the phenotypes of certain mutant mice, including curly tail (Seller et al 1979) and Splotch (Kapron-Bras and Trasler 1984 …”