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

患有唐氏综合症的婴儿约占新生儿总数的1/700。这种综合征的产生是因为唐氏综合症患者有一份额外的21号染色体。唐氏综合症是最常见的精神发育迟滞的原因，它与其他许多不同的特征一起发生，比如特定的心脏缺陷或免疫系统的异常。为了找出人类21号染色体上哪些基因导致了唐氏综合症的不同方面，我们建立了唐氏综合症的小鼠模型。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，以准确地计算出这只小鼠中存在哪些基因，以及它们何时何地被打开。然后，我们希望通过添加一个标记来改进小鼠模型，该标记允许我们区分哪些细胞包含额外的染色体。我们还想去研究这些小鼠的大脑，看看小鼠与人类唐氏综合症有多相似，并最终试图找出哪些是导致唐氏综合症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，着眼于治疗唐氏综合症的某些方面，也将告诉我们在非唐氏综合症人群中发生的完全相同的疾病。

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.