Early morphological abnormalities in splotch mouse embryos and predisposition to gene‐ and retinoic acid‐induced neural tube defects

Abstract

Genetic and environmental factors contribute to an individual's neural tube defect liability. In the mouse, the gene mutation Splotch (Sp) causes a pigmentation defect in heterozygotes while homozygotes have spina bifida ± exencephaly. Splotch homozygotes, heterozygotes, and wild‐type embryos were examined for somite number, anterior neuropore closure, and posterior neuropore length. The aim was to distinguish potentially affected homozygotes early in pathogenesis and find a morphological basis for increased teratogen susceptibility in heterozygotes. Posterior neuropore closure as well as anterior neuropore closure was significantly delayed in potentially affected Sp as compared to wild‐type litter embryos exceeding the incidence found in day‐10‐diagnosed homozygotes. Part of this excess was attributed to a transient delay in heterozygotes which in turn might predispose to retinoic acid‐induced neural tube defects. This idea was supported by an outcross of Sp heterozygote males by inbred SWV females and wild‐type males by SWV where a significant increase in retinoic acid‐induced neural tube defects was found in Sp carrier litters.