CARDIOVASCULAR DISEASE GENES IN ANIMAL MODELS

这项提议的目标是衍生出一个多潜能的胚胎 兔干细胞系构建兔的实验研究 人类疾病的模型。细胞系将从内部细胞派生而来 兔胚胎移植后在适当条件下的大量细胞 饲养层和生长和维护所需的其他条件 细胞的未分化(多潜能)状态通过 连载文章。将使用Y标识雄性(XY)ES系 染色体特异的探针，其特征在于： (1)形成类胚体和分化为细胞型的能力 具有三个胚层的特点， (2)正常兔胚胎移植后定植能力的研究 进入受体囊胚，以产生嵌合动物，以及 终于到了 (3)人类遗传相关基因靶向突变的角蛋白 精神错乱。 将胚胎干细胞技术扩展到比小鼠更大的物种 为目前建立人类动物模型的努力增加了一个新的维度 遗传病。这样的动物将促进我们对基本知识的理解 涉及遗传病的机制，并为 为他们的治疗提供新的药理学或遗传学方法。 特别是，这些动物将比老鼠更多才多艺 许多类型的生理调查，并可能复制更多 准确地说是某些基因缺陷导致的人类表型。

The objective of this proposal is to derive a pluripotential embryonic stem (ES) cell line from the rabbit for the purpose of creating rabbit models of human disease. Cell lines will be derived from the inner cell mass cells of explanted rabbit embryos in the presence of appropriate feeder layers and other conditions necessary for growth and maintenance of the undifferentiated (pluripotential) state of the cells through serial passage. Male (XY) ES lines will be identified using a Y chromosome-specific probe, and characterized in terms of: (1) Ability to form embryoid bodies and to differentiated into cell types characteristic of the three germ layers, (2) Ability to colonize the normal rabbit embryo following introduction into recipient blastocysts for generation of chimeric animals, and finally (3) Ceratin of targeted mutations in genes implicated in human genetic disorders. Extension of ES cell technology into a species larger than the mouse will add a new dimension to current effort to generate animal models of human genetic diseases. Such animals will advance our understanding of basic mechanisms involved in genetic diseases, and provide model systems for advancing new pharmacologic or genetic approaches to their treatment. In particular, these animals will be more versatile than the mouse for many types of physiological investigations, and may reproduce more accurately the human phenotype resulting from certain gene defects.