IMPC: Investigating the brain role of Setd1a in relation to schizophrenia and developmental disorders

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Many psychiatric disorders are, in part, heritable. Genetic studies of these psychiatric disorders are providing valid leads to investigate their biology, with the hope that this may one day lead to therapies. Genetic risk for many mental disorders divides into a large number of common
variants that have very small, but cumulative effects; and several very rare, damaging variants. Recent technological advances have allowed us to identify rare genetic mutations that have strong consequences for complex brain diseases. Member of the MRC Centre for Neuropsychiatric
Genetics and Genomics in Cardiff (CNGG) were part of an international team that identified such a rare mutation contributing to schizophrenia and other developmental disorders in a gene called SET domain 1a (SETD1A). SETD1A encodes an enzyme that can regulate the activity of other genes. However, the specific brain functions of this gene remain unknown. We want to examine what SETD1A does through replicating the mutation in a mouse model by removing one of the two copies of this gene in the mouse genome. However, we will limit this genetic mutation to the brain, in order to clearly examine the role SETD1A plays in the brain. This grant will help us to generate and develop this mouse model, and to start the early characterisation.