Functional analysis of the X-linked Hypopituitarism (XH) gene SOX3

许多对正常身体功能至关重要的过程，如生长、应对压力的能力、性器官发育和新陈代谢，都是由脑下垂体控制的。这个器官位于大脑的底部，通过释放六种不同的激素来调节这些身体功能。脑垂体腺的形成发生在胎儿的发育过程中。这个过程需要一组特定的基因来塑造脑下垂体，并允许荷尔蒙分泌细胞的出现。这些脑下垂体形成基因的变化会导致新生儿脑下垂体功能障碍(垂体功能减退)。在严重的情况下，脑下垂体没有完全形成，这些婴儿病情严重，在某些情况下无法存活。我们正在研究遗传性垂体功能低下症的家庭，在这种家庭中，只有男性孩子会受到影响。这种疾病是由于X染色体上存在额外的遗传物质(DNA)所致。我们最近发现，其中一个重复的基因SOX3导致了这种疾病。这项建议的总体目标是了解SOX3是如何通过为这种疾病建立小鼠模型来导致垂体功能低下的。对这一小鼠模型的分析将有助于我们了解垂体功能减退的临床特征，并可能使我们能够识别与这种疾病相关的以前没有特征的解剖学缺陷。最终，我们希望利用这个小鼠模型来开发新的和改进的治疗垂体腺功能低下症的方法。

Many of the processes that are essential for normal bodily function such as growth, the ability to cope with stress, sexual organ development and metabolism are controlled by the pituitary gland. This organ is located at the base of the brain and regulates these bodily functions through the release of six different hormones. Formation of the pituitary gland occurs during development of the foetus. This process requires a specific set of genes that shape the pituitary and allow the hormone-secreting cells to arise. Changes in these pituitary formation genes results in dysfunction of the pituitary (hypopituitarism) in newborn babies. In severe cases, where the pituitary has failed to form completely, these babies are extremely ill and in some instances do not survive. We are studying families with an inherited form of hypopituitarism in which only male children are affected. This disorder is due to the presence of an extra piece of genetic material (DNA) on the X chromosome. We have recently discovered that one of the duplicated genes, SOX3, causes this disorder. The overall aim of this proposal is to understand how SOX3 causes hypopituitarism by generating a mouse model for this disorder. Analysis of this mouse model will help us to understand the clinical features of hypopituitarism and may allow us to identify previously uncharacterised anatomical defects associated with this disorder. Ultimately,we hope to develop new and improved therapies for hypopituitarism using this mouse model.