Differential sensitivity of mouse neural crest cells to ethanol-induced toxicity

Neural crest cells (NCCs) have been identified as an important target popul ation relative to ethanol-induced teratogenicity in both mouse and avian mo dels. Additionally, whole embryo culture mouse models have shown strain-rel ated differences in sensitivity to ethanol-induced damage following acute e xposure during early NCC development. That differential sensitivity of NCCs may contribute to these strain differences has been unexplored. For this p urpose, cultured NCCs from an inbred mouse strain (C57BL/6J; C57) that is m ore sensitive to ethanol-induced teratogenicity than an outbred strain (ICR ) were compared. This study showed that the incidence of cell death was sig nificantly higher for the C57 NCCs than those from the ICR strain at all et hanol concentrations tested, and as early as 12 hours after initial exposur e to 100 mM ethanol. The lateral mobility of the membrane lipids was faster and the membrane GM1 content was lower in C57 cells than ICR cells both un der control conditions and at all doses and times tested. Ethanol exposure resulted in significant increases in the membrane lipid lateral mobility, a nd decreases in the membrane GM1 content that occurred in a dose and time-d ependent manner in the NCCs from both strains. A significant correlation wa s found between the GM1 content and lateral mobility of the membrane lipids , the lateral mobility of membrane lipids and cell viability, as well as th e GM1 content and cell viability in the NCCs from both strains. These resul ts suggest that different strain sensitivities to ethanol-induced teratogen city may lie, at least in part, in the interstrain differential response of the NCC population and that the vulnerability of the NCCs to ethanol-induc ed death may be related to their endogenous membrane GM1 content. (C) 2000 Elsevier Science Inc. All rights reserved.