Genetics and morphology of the middle ear ossicles in the developing mouse embryo

发育中的小鼠胚胎中耳小骨的遗传学和形态学

• 批准号: G0501037/1
• 负责人: Abigail Tucker
• 金额: $ 27.68万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0501037%2F1
• 关键词: Genetics; morphology; middle; ear; ossicles

I am interested in researching how the middle ear ossicles develop. Defects in these ossicles, such as fusion, are fairly common and lead to hearing problems. These defects can be seen by using CT (computed tomography) scans, which allow assessment of the patient s suitability for corrective ear surgery. The middle ear is composed of three ossicles that form a chain linking the ear drum with the inner ear. The three ossicles are connected by joints, which can be malformed or absent, resulting in fusion of the middle ear and hearing loss. In these patients it is unclear how the defects observed arose. This is due to a lack of information available with respect to formation of these joints during normal development.This research attempts to correct this deficit in our knowledge by investigating the middle ear, first in normal and then in mutant mouse embryos. Development of the mouse middle ear has been shown to be similar to that of humans and therefore information obtained from using mouse models can be directly related to human patients. I plan to concentrate mainly on the first two ossicles and joint region, as this is the region where defects most often occur. We would first like to know: sum How the joint forms sum What genes are involved in joint formation sum How is the position of the joint determined sum How do each of the three ossicles develop their individual specification (ie their difference from each other) during normal embryonic development.Having identifies how this region of the middle ear normally forms we will use this information to investigate cases where there is an abnormality. For this we will be analysing a mouse embryo that has a mutation in a gene called TCOF1. Patients with defects in this gene develop Treacher Collins syndrome (TCS) which is associated with a fused middle ear and hearing loss in almost 100% of cases. This work should give a clear picture of how the middle ear defects seen in TCS occur during embryology. Ultimately, such information may help patients with TCS by allowing for a more informed decision when the option for surgery is discussed.

我对研究中耳听骨是如何发育的很感兴趣。这些听小骨的缺陷，如融合，是相当常见的，并会导致听力问题。这些缺陷可以通过CT(计算机断层扫描)扫描来看到，这可以评估患者S是否适合进行矫正耳部手术。中耳由三个听小骨组成，它们形成一个链条，将鼓膜与内耳连接起来。三个听小骨由关节连接，关节可能畸形或缺失，导致中耳融合和听力损失。在这些患者中，尚不清楚观察到的缺陷是如何产生的。这是由于缺乏关于这些关节在正常发育过程中形成的信息。这项研究试图通过研究中耳来纠正我们知识中的这个缺陷，首先是在正常的小鼠胚胎中，然后是在突变的小鼠胚胎中。小鼠中耳的发育已被证明与人类相似，因此通过使用小鼠模型获得的信息可能与人类患者直接相关。我计划主要集中在前两个听小骨和关节区域，因为这是最常发生缺陷的区域。我们首先想知道：关节形式是如何形成的，哪些基因参与了关节的形成和，关节的位置如何决定和，三个听小骨在正常的胚胎发育过程中如何形成各自的特点(即它们之间的差异)。在确定了中耳这一区域的正常形成后，我们将利用这些信息来调查存在异常的情况。为此，我们将分析一种名为TCOF1基因突变的小鼠胚胎。该基因缺陷的患者会患上Treacher Collins综合征(TCS)，几乎100%的病例与中耳融合和听力损失有关。这项工作应该能清楚地描绘出TCS中的中耳缺陷是如何在胚胎学期间发生的。最终，当讨论手术选择时，这些信息可能会帮助TCS患者做出更明智的决定。