METHANOL CAUSES POSTERIORIZATION OF CERVICAL-VERTEBRAE IN MICE

Inhalation of methanol by pregnant mice before gestation day nine (gd 9) produces fetal skeletal alterations, principally in the cervical re gion. The appearance of these defects suggests homeotic shifts in segm ent identity, patterning, or both. To explore this possibility, detail ed morphological analyses of the effects of methanol on fetal skeletal development were done. Pregnant mice were gavaged with 0, 4.0, or 5.0 g/kg methanol (MeOH) split in two doses on gd 7, the most sensitive d ay for induction of skeletal alterations with methanol. Dams were kill ed on gd 18 and the fetuses were counted, weighed, and examined extern ally. Fetuses were double stained with alcian blue and alizarin red fo r examination of cartilaginous and ossified vertebral and rib characte ristics, and in selected fetuses cervical vertebrae were disarticulate d for more detailed analysis. Observations indicative of methanol-indu ced homeotic transformations were as follows: [GRAPHICS] Examination o f disarticulated vertebrae revealed foramina and other distinguishing characteristics on vertebrae anterior to those on which they normally appear. These results demonstrate that maternal methanol exposure can alter segment patterning in the developing mouse embryo, producing pos teriorization of cervical vertebrae. (C) 1997 Wiley-Liss, Inc.