Identification and characterization of a novel splice variant of disrupted in schizophrenia 1 (Disc1)

抄録

Alternative splicing (AS) contributes to the generation of distinct mRNAs from the same pre-mRNA. This mechanism is highly conserved in eukaryotes and yields proteomic diversity. Furthermore, AS can be tissue- and developmental stage-specific and is an important process in the development of the central nervous system. Although these features suggest that AS variants contribute the complexity of the brain, the characteristics of most AS variants are unclear. Therefore, it is important to identify and examine novel AS variants in neuronal tissues to fully understand neuronal functions. We have identified a novel AS variant of murine disrupted in schizophrenia 1 (Disc1), a neural developmental gene. This variant lacks exon 2 and is named 'ΔE2'. We also show differences in the expression levels and localization patterns between ΔE2 and full length Disc1 (FL) in the murine brain. Differences in the subcellular localization patterns of both isoforms in cultured SK-N-SH cells suggest that ΔE2 has different functions compared with those of FL. Further functional analysis of ΔE2 may indicate additional roles of Disc1, and may further our understanding of the developmental mechanisms for neurodevelopmental disorders such as schizophrenia.