The role of the calcineurin negative regulator, DSCR1, in heart development and hypertrophy.

年轻人的先天性心脏缺陷和晚年的心脏病给我们的社会带来了疾病、残疾和死亡方面的沉重负担，在保健预算方面也非常昂贵。心脏瓣膜发育失败和心脏穿孔是非常常见的异常，发生在所有活产婴儿的近1%。大约44%的唐氏综合症患者也存在这种类型的异常，这是由于个体携带了额外的21号染色体。因此，很可能是位于人类21号染色体上的一个基因导致了这种病理，事实上，我们在鉴定可能导致唐氏综合症中观察到的心脏缺陷的基因方面的工作，导致了一个名为DSCR1的基因的发现。DSCR1是一种生物通路的负调节因子，当它在心脏中受到干扰时，可导致发育性心脏畸形，类似于唐氏综合症的类型，当过度刺激时，可导致高血压和心脏病患者的心脏异常生长。如果我们要对心脏缺陷和疾病的潜在治疗方法设计做出理性的决定，我们首先需要了解这些生物途径是如何工作的，以及DSCR1等分子是如何调节它们的。我们的目标是通过培养缺乏该基因的小鼠来研究DSCR1的功能，看看缺失时会发生什么，以及过度表达该基因的小鼠来研究DSCR1水平升高的后果，类似于唐氏综合症的情况。

Congenital heart defects in the young and heart disease later in life place a heavy burden on our society in terms of illness, disability and death and are very costly in terms of the health care budget. Failure of heart valve development and holes in the heart, are very common abnormalities occurring in nearly 1 % of all live births. This type of anomaly is also observed in about 44 % of individuals with Down syndrome, which results when individuals carry an extra copy of chromosome 21. Thus, it is likely that a gene located on human chromosome 21 contributes to this pathology and indeed our work on the identification of genes with the potential to cause the heart defect observed in Down syndrome, has led to the discovery of a gene called DSCR1. DSCR1 is a negative regulator of a biological pathway which when disturbed in the heart can lead to developmental heart malformations, similar to the type seen in Down syndrome, and when over stimulated can result in the abnormal growth of the heart seen in humans with hypertension and heart disease. If we are to make rational decisions about the design of potential treatments for heart defects and disease, we firstly need to understand how these biological pathways work and how molecules such as DSCR1 regulate them. We aim to investigate how DSCR1 functions by generating mice that lack the gene, to see what happens when it is missing and mice over expressing the gene to investigate the consequences of elevated levels of DSCR1 analogous to the situation in Down syndrome.