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，科普压力的能力，性器官发育和新陈代谢都由脑垂体控制。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。脑下垂体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垂体，并允许垂体分泌细胞出现。这些垂体形成基因的变化导致新生儿垂体功能障碍（垂体功能减退症）。在严重的情况下，垂体未能完全形成，这些婴儿病情严重，在某些情况下无法生存。我们正在研究一种遗传性垂体功能减退症的家庭，其中只有男孩受到影响。这种疾病是由于X染色体上存在额外的遗传物质（DNA）。我们最近发现，其中一个复制基因SOX 3导致了这种疾病。该提案的总体目标是通过生成这种疾病的小鼠模型来了解SOX 3如何导致垂体功能减退。对这种小鼠模型的分析将帮助我们了解垂体功能减退症的临床特征，并可能使我们能够识别与这种疾病相关的以前未描述的解剖缺陷。最终，我们希望使用这种小鼠模型开发新的和改进的垂体功能减退症疗法。

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.