Novel alternatively-spliced exons of the VRK2 gene in mouse brain and microglial cells.

Common sequence variations in the VRK2 gene contribute to genetic risk for various psychiatric diseases including schizophrenia and major depressive disorder. Despite the clear importance of studying the regulation and function of VRK2 for understanding the causes of these diseases, the organisation and expression of the gene remain poorly characterised. Using reverse-transcriptase-PCR, we have amplifed exons of Vrk2 mRNA from regions of mouse brain, and from different cell classes comprising neurones, astrocytes and microglial cells. We find that Vrk2 mRNA is expressed in all cell types, and that the splicing of the mouse Vrk2 gene is much more complex than previously appreciated. In addition to the predicted alternative splicing (absence/presence) of the penultimate 3 prime exon, we also detected a variety of 5 prime structures, including two novel exons spanning the first characterised exon (exon 1), which we term exons 1a and 1b. While expressed in neurones and astrocytes, exon 1b was not expressed in microglial cells. Expression of transcripts containing exon 1a in microglia was increased by immune stimulation. An additional truncated transcript lacking 7 central exons was also identified. As with the human gene, the results confirm complex patterns of alternative splicing which are likely to be relevant for understanding the physiological and pathological function of the gene in the CNS.