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

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 在美国出生的每33个婴儿中就有一个有先天缺陷，其中许多是由于 暴露于环境致畸剂。例如，乙醇（EtOH）消耗在 妊娠导致发育中的胎儿出现一系列可预测的异常， 胎儿酒精谱系缺陷（FASD）这些先天性畸形包括 颅面畸形，心脏缺陷，神经管缺陷，小眼症，低出生体重， 和学习障碍。怀孕期间体温过高（由于发烧或其他原因） 产生类似的发展影响。小眼症（眼睛缩小），一般 90%的FASD病例均伴有严重视力障碍，并且还 产妇体温过高的典型症状我们的长期目标是确定 环境致畸剂引起发育缺陷的机制 视觉系统我们目前的目标是检验共同的遗传因素 是胚胎对环境致畸物敏感性的基础在人类中，遗传因素 已知有助于保护作用或对致畸损伤的易感性。为 例如，在校正了母亲饮酒量的差异后，FASD是7.6倍 非洲裔儿童比其他种族群体更有可能。 我们使用胚胎斑马鱼作为我们的发育研究的模型系统。大 可以产生大量易于操作的透明胚胎， 分子资源丰富。用EtOH处理的斑马鱼胚胎显示发育 与人类FASD中观察到的异常相似，包括小眼症和其他 视觉系统异常温度升高的胚胎也显示出 小眼症这些致畸作用是高度菌株特异性的，因为某些菌株 斑马鱼对乙醇和高温比其他鱼类更敏感。

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.