IDENTIFICATION OF A GROWTH ARREST-SPECIFIC (GAS-5) GENE BY DIFFERENTIAL DISPLAY AS A CANDIDATE GENE FOR DETERMINING SUSCEPTIBILITY TO HYPERTHERMIA-INDUCED EXENCEPHALY IN MICE

Neural tube defects (NTDs) are among the most common congenital malfor mations, affecting approximately 1 per 1,000 liveborn infants in the U nited States [Nakano, 1973, Richards et al., 1972]. Maternal exposure to hyperthermia, either through recreational sources or due to an infe ctious agent, is thought io account for approximately 10% of observed NTD cases. The specific genes conferring susceptibility or resistance to hyperthermia-induced NTDs have not been identified. This study used differential display-polymerase chain reaction (DD-PCR) to characteri ze alterations in gene expression in the anterior embryonic neural tub e of two highly inbred murine strains (SWV/Fnn, LM/Bc/Fnn) known to di ffer in their genetically determined susceptibility to heat-induced NT Ds. Herein, we report the neural tube-specific differential expression of the growth arrest specific (gas 5) gene In the highly susceptible SWV/Fnn strain during neural tube closure (NTC). Although the the expr ession of gas 5 did appear io be altered by the teratogenic heat treat ment, its spatial and strain-specific pattern of expression makes it a n excellent candidate gene responsible for the observed genetic differ ences in NTD susceptibility between these two inbred murine strains. ( C) 1997 Wiley-Liss Inc.