You are here:
METHANOL EXPOSURE DURING GASTRULATION CAUSES HOLOPROSENCEPHALY, FACIAL DYSGENESIS AND CERVICAL VERTEBRAL MALFORMATIONS IN C57BL/6J MICE
Citation:
Rogers, J M., K. C. Brannen, R M. Zucker, B D. Barbee, AND S J. Degitz. METHANOL EXPOSURE DURING GASTRULATION CAUSES HOLOPROSENCEPHALY, FACIAL DYSGENESIS AND CERVICAL VERTEBRAL MALFORMATIONS IN C57BL/6J MICE. BIRTH DEFECTS RESEARCH PART B: DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY. John Wiley & Sons, Ltd., Indianapolis, IN, 71(2):80-88, (2004).
Impact/Purpose:
To evaluate craniofacial malformations induced in the C57BL/6J mouse by methanol
Description:
Exposure of pregnant CD-1 mice to methanol during the period of gastrulation results in exencephaly, cleft palate, and cervical vertebra malformations (Rogers and Mole, 1997, Teratology 55, 364). C57BL/6J mice are sensitive to the teratogenicity of ethanol; fetuses of this strain exhibit the holoprosencephaly spectrum of malformations after maternal exposure during gastrulation (Sulik et al., 1988, Development 103 Suppl., 213). The sensitivity of C57BL/6J mice to methanol-induced teratogenesis has not been described. Here, pregnant C57BL/6J mice were administered two i.p. injections totaling 3.4 or 4.9 g/kg methanol or dH2O four hrs apart on gestation day (GD) 7. No maternal intoxication was apparent, but the high dosage level caused a transient deficit in maternal weight gain. On GD 17, litters were examined for number live and resorbed, fetuses were weighed as a litter and examined externally, and all fetuses were double stained for skeletal analysis. The number of live fetuses per litter was reduced at both dosages of methanol, and fetal weight was lower in the high dosage group. Craniofacial defects were observed in 55.8% of fetuses in the low dosage group and 91.0% of fetuses in the high dosage group, including micro/anophthalmia, holoprosencephaly, facial clefts and gross facial agenesis. Skeletal malformations, particularly of the cervical vertebrae, were observed at both dosages of methanol, and were similar to those previously reported in the CD-1 mouse following methanol exposure. The types of craniofacial malformations induced in the C57BL/6J mouse by methanol suggest that methanol and ethanol may have common modes of action.