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

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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.