Molecular genetics and brain in the Tc1 mouse model of Down syndrome

患有唐氏综合症的婴儿约占700名新生儿中的1名。这种综合症的出现是因为患有唐氏综合症的人有一个额外的21号染色体拷贝。唐氏综合症是最常见的已知原因的智力迟钝，并发生沿着许多其他更多变的特征，如特定的心脏缺陷或异常的免疫系统。试图找出哪些基因在人类染色体21引起的不同方面的综合症，我们创建了一个小鼠模型唐氏综合症。这是一种独特的小鼠品系，它确实概括了唐氏综合症的特征。我们现在正在申请资金，以弄清楚这只小鼠体内存在哪些基因，以及它们在何时何地被激活。然后，我们希望通过添加一个标记来完善小鼠模型，使我们能够分辨哪些细胞含有额外的染色体。我们还想研究这些小鼠的大脑，看看小鼠与人类唐氏综合症的相似程度，并最终试图找出哪些是产生唐氏综合症中某些特定大脑变化的重要基因。这项研究将帮助我们更多地了解唐氏综合症发生的原因，从长远来看，对该综合症的某些方面进行治疗，也会告诉我们发生在非唐氏综合症人群中的完全相同的疾病。

Babies with Down syndrome account for about 1 in 700 births. The syndrome arises because people with Down syndrome have an extra copy of chromosome 21. Down syndrome is the most common known cause of mental retardation, and occurs along with many other more variable features, such as specific heart defects or abnormalities of the immune system.To try to find out which genes on human chromosome 21 give rise to the different aspects of the syndrome, we created a mouse model of Down syndrome. This is a unique mouse strain, and it does recapitulate the features of Down syndrome. We are now applying for funding to work out exactly which genes are present in this mouse, and when and where they are switched on. We then want to refine the mouse model by adding in a marker that allows us to tell which cells contain the extra chromosome. We also want to go to study the brain of these mice, to see how closely the mouse parallels human Down syndrome, and ultimately to try to work out which are the important genes for producing some of the specific brain changes that are seen in Down syndrome.This research will help us understand more about why Down syndrome occurs, with a long-term view to therapy for some aspects of the syndrome, and will also tell us about exactly the same disorders that occur in the non-Down syndrome population.