CARDIOVASCULAR DISEASE GENES IN ANIMAL MODELS

这项建议的目的是获得一个多能胚胎， 干（ES）细胞系从兔子的目的，创造兔 人类疾病的模型。 细胞系将来自内部细胞 在适当的条件下， 饲养层和其他生长和维持所需的条件 细胞的未分化（多能性）状态， 连续传代 雄性（XY）ES系将使用Y 染色体特异性探针，并且其特征在于： (1)形成胚状体和分化成细胞类型的能力 三个胚层的特征， (2)引入后在正常兔胚胎中定殖的能力 用于产生嵌合动物，和 最后 (3)人类遗传病相关基因靶向突变确定 紊乱 将胚胎干细胞技术扩展到比小鼠更大的物种中， 为目前产生人类的动物模型的努力增加了一个新的维度 遗传病 这些动物将促进我们对基本的 遗传疾病的机制，并提供模型系统， 推进新的药理学或基因治疗方法。 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，是由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.