Vertebrate Limb Development 2

正常心脏形成中的先天性心脏病是最常见的出生缺陷，每120名活产婴儿中就有1名发生。如果不加以纠正，这些缺陷可能会对生活质量产生严重的衰弱影响，严重的情况下会导致过早死亡。其他不太危及生命的出生缺陷也大大降低了受影响个体的生活质量。其中，肢体缺损最为常见。我们有兴趣研究导致正常心脏和肢体形成严重异常的两种人类综合征的原因。Holt-Oram综合征（HOS）患者的心脏和四肢严重畸形，尺乳综合征（UMS）患者的四肢和乳腺发育异常。|在每一种综合征中，单个基因中遗传信息的破坏足以导致所有相关的异常。有了这些关于每种综合征确切遗传原因的知识，我们建议调查这些疾病的潜在生物学。使用小鼠和鸡，我们正在生成综合征模型，这些模型提供了一种强大的方法来了解正常基因功能的丧失如何导致心脏和肢体形成的破坏。在这两种动物模型中，心脏和四肢的发育与我们的相似，每种动物模型都有我们可以利用的实验优势。了解这些综合征的起源将提供重要的信息，以设计更有效的诊断和纠正治疗人类患者。

Abnormalities in normal heart formation are the most common birth defect, occurring in 1 in 120 live births. If uncorrected, these defects can have serious debilitating effects on quality of life and in severe cases lead to premature death. Other less life-threatening birth defects also dramatically decrease quality of life in affected individuals. Among these, limb defects are the most common. We are interested in studying the causes of two human syndromes that lead to serious abnormalities in normal heart and limb formation. Patients with Holt-Oram Syndrome (HOS) have severely malformed hearts and limbs and those with Ulnar-Mammary Syndrome (UMS) are afflicted with abnormal limb and mammary gland development.|In each syndrome the corruption of the genetic information in a single gene is sufficient to cause all of the associated abnormalities. Armed with this knowledge of the exact genetic cause of each syndrome we propose to investigate the underlying biology of these diseases. Using the mouse and chicken, we are generating syndrome models that provide a powerful method to understand how loss of normal gene function leads to the disruption of heart and limb formation. In both animal models, the development of the heart and limbs occurs in a similar manner to our own and each animal model has experimental advantages we can exploit. Understanding the genesis of these syndromes will provide information vital in order to devise more effective diagnostic and corrective treatments in human patients.