P.1.a.002 Association study of −1727 A/T and −50C/T GSK-3 beta gene polymorphism with suicidal behaviour in depressed patients

Abstract

Glycogen synthase kinase-3α and -3β (GSK-3α and -3β) are multi-substrate, serine/threonine-specific kinases that can phosphorylate microtubule-associated protein tau and other neuronal proteins. In this study, the expression level and mRNA distribution of two GSK-3 isoforms, GSK-3α and -3β in mice were investigated. Northern blot analyses indicated that GSK-3α mRNA is encoded by a 2.5-kb transcript in adult tissues, whereas a 4.1-kb transcript was found in neonatal tissues. The GSK-3β mRNA is encoded by a 1.6-kb transcript in the testis and a 7.6-kb transcript in the brain, and in many other adult tissues, but not neonatal tissues. Western blot analyses demonstrated that GSK-3β protein was mainly expressed in the brain and heart, whereas GSK-3α was highly expressed in the brain, heart, and testis. A non-radioactive in situ hybridization study using specific digoxigenin-labeled RNA probes showed that GSK-3α and -3β mRNAs were found in many brain regions, and were especially abundant in the hippocampus, cerebral cortex, and the Purkinje cells of the cerebellum. This implies the importance of GSK-3α and -3β for brain function. The differential expression of GSK-3α and -3β mRNAs as well as proteins in other tissues indicate that they play different roles in cellular functions and the developmental process.