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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在美国出生的婴儿中，每33个中就有一个有出生缺陷，其中许多是由于 暴露在环境致畸物质中。例如，乙醇(Etoh)在 怀孕会导致发育中的胎儿出现一系列可预见的异常。 作为胎儿酒精光谱缺陷(FASD)。这些先天畸形包括 头面部畸形，心脏缺陷，神经管缺陷，小眼炎，低出生体重， 和学习障碍。孕期体温过高(因发烧或其他原因) 导致类似的发展影响。小眼炎(眼睛缩小)，一般 伴随着严重的视力障碍，在所有FASD病例中显示出90%，也 母亲体温过高的病例的特征。我们的长期目标是确定 环境致畸致畸机制(S) 视觉系统。我们目前的目标是验证这样一个假设，即共同的遗传因素 胚胎对环境致畸性的敏感性是基础。在人类中，遗传因素 已知对致畸侮辱有保护作用或易感性。为 例如，在校正了母亲饮酒的差异后，FASD是7.6倍 与其他种族群体相比，非洲裔儿童更有可能发生这种情况。 我们使用胚胎斑马鱼作为发育研究的模型系统。大型 可以产生许多易于操作的透明胚胎，并且遗传和 分子资源丰富。乙醇处理的斑马鱼胚胎发育良好 类似于人类FASD的异常，包括小眼球和其他 视觉系统异常。温度升高的胚胎也表现出 小眼炎。这些致畸作用是高度特定于菌株的，因为一些菌株 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.