Cloning of the promoter of NDE1, a gene implicated in psychiatric and neurodevelopmental disorders through copy number variation

• The complex promoter system of the neurodevelopmental gene NDE1 is cloned.
• This gene is implicated in major mental illness through copy number variation.
• In neuroblastoma cells, one NDE1 transcript is predominantly expressed.
• The importance of the 5′ UTR of this transcript is determined.
• These will facilitate the study of NDE1 duplication in major mental illness.

Copy number variation at 16p13.11 has been associated with a range of neurodevelopmental and psychiatric conditions, with duplication of this region being more common in individuals with schizophrenia. A prominent candidate gene within this locus is NDE1 (Nuclear Distribution Element 1) given its known importance for neurodevelopment, previous associations with mental illness and its well characterized interaction with the Disrupted in Schizophrenia 1 (DISC1) protein. In order to accurately model the effect of NDE1 duplication, it is important to first gain an understanding of how the gene is expressed. The complex promoter system of NDE1, which produces three distinct transcripts, each encoding for the same full-length NDE1 protein (also known as NudE), was therefore cloned and tested in human cell lines. The promoter for the longest of these three NDE1 transcripts was found to be responsible for the majority of expression in these systems, with its extended 5′ untranslated region (UTR) having a limiting effect on its expression. These results thus highlight and clone the promoter elements required to generate systems in which the NDE1 protein is exogenously expressed under its native promoter, providing a biologically relevant model of 16p13.11 duplication in major mental illness.