H-2 haplotype and heterochronic orofacial morphogenesis in congenic mice: consideration as a possible explanation for differential susceptibility to teratogenesis.

For over 40 years it has been known that genetically different inbred strains of mice have different degrees of susceptibility to corticosteroid-induced cleft palate. Gene(s) at or near the H-2 region on chromosome 17 have been implicated. One postulated explanation is that the strain difference in susceptibility is not related to differential corticosteroid action, but to differences in normal developmental pattern. Studies have demonstrated significant quantitative differences between inbred strains for a number of growth variables relative to palatal development. It is also known that there are genes at or near the H-2 complex that influence pre- and post-implantation development. Thus, we sought to determine the relationship in H-2 congenic mice between haplotype differences and variation in normal orofacial development. Morphometric analyses of the palatal region in serially sectioned E13 and E17 B10 and B10.A mice were completed. We were able to find some evidence for H-2 haplotype related phenotypic differences, but these differences are less than compelling as an explanation for haplotype-dependent susceptibility differences. A more likely explanation is GR-mediated differential corticosteroid responsiveness and its consequent effects on palatal shelf growth.