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

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.

DS is the most common known form of mental retardation, and also has at least 80 other phenotypic aspects in different tissues. We have created a unique mouse model of DS, the Tc1 transchromosomic mouse. We now wish to investigate the molecular genetics of this mouse in detail and to go on to improve the model and start to study the brain in this animal.