COBRE: UID: PILOT: GENETIC FACTORS UNDERLYING SUSCEPTIBILITY TO BIRTH DEFECTS

这个子项目是众多研究子项目之一

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. One in 33 babies born in the United States has a birth defect, many of which are the result of exposure to environmental teratogens. For example, ethanol (EtOH) consumption during pregnancy results in a spectrum of predictable abnormalities in the developing fetus, referred to as Fetal Alcohol Spectrum Defects (FASD). These congenital malformations include craniofacial anomalies, heart defects, neural tube defects, microphthalmia, low birth weight, and learning disabilities. Hyperthermia during pregnancy (due to fever or other causes) results in similar developmental impacts. Microphthalmia (reduced eye size), generally accompanied by severe visual impairment, is exhibited in 90% of all cases of FASD and is also characteristic in cases of maternal hyperthermia. Our long-term goal is to determine the mechanism(s) through which environmental teratogens cause developmental defects in the visual system. Our current objective is to test the hypothesis that common genetic factors underlie embryonic susceptibility to environmental teratogens. In humans, genetic factors are known to contribute protective effects or susceptibility to teratogenic insults. For example, after correcting for differences in maternal alcohol consumption, FASD is 7.6 times more likely in children of African descent than in other racial groups. We use the embryonic zebrafish as a model system for our developmental studies. Large numbers of easily manipulated, transparent embryos can be generated, and genetic and molecular resources are abundant. Zebrafish embryos treated with EtOH show developmental abnormalities similar to those seen in human FASD, including microphthalmia and other visual system anomalies. Embryos subjected to increased temperature also display microphthalmia. These teratogenic effects are highly strain-specific, in that some strains of zebrafish are more sensitive to EtOH and hyperthermia than others.