Loss of myelinated axons is specific to the central nervous system in a mouse model of the fetal alcohol syndrome

We have previously developed a mouse model of the fetal alcohol syndrome, the outcome of which is a late loss of myelinated axons in the optic nerve of offspring of alcohol-treated mice between 9 and 15 wk of age. We have extended this study to investigate whether this axon loss is stable and specific to the central nervous system. Pregnant female (C57BL/6/Wlds x CBA) F1 mice were injected intraperitoneally with a single dose of a 25% solution of ethanol (v:w), on d 12 of gestation. Control animals were given a similar volume of saline at the same time. Litters were taken at 12 (n = 18) and 23 (n = 26) wk of age. Optic nerves only from 12-wk-old, and optic, tibial and saphenous nerves from 23-wk-old mice were removed. A systematic, random sampling method was used to estimate the cross-sectional area of whole nerves from semi thin sections, and the numbers and diameters of myelinated axons from ultrathin sections. There were no differences for the optic nerves of 12-wk-old alcohol-treated and control animals. Optic nerves from the alcohol-treated group at 23 wk had smaller cross-sectional areas and approximately 17% fewer myelinated axons than control nerves. These results confirm that axon loss occurs between 12 and 15 wk, and demonstrate that there is no additional loss of myelinated axons between 15 and 23 wk. In contrast, there were no significant differences in cross-sectional area, number of myelinated axons or axon calibre spectra for the tibial and saphenous nerves between the alcohol-treated and control groups. There was thus no evidence of a peripheral neuropathy as has been observed in chronic alcoholic subjects. In this 'binge' model of the fetal alcohol syndrome, a carefully timed dose of alcohol is administered during pregnancy to coincide with a critical period of development of the visual system. The result is a teratogenic effect which is specific to the central nervous system, stable and reproducible, with no obvious effect on the peripheral nervous system.