The fusions are C-terminal fusions that use the same transcription and translation signals for their expression. In the cases where we have examined accumulation of the fusion proteins after induction, the proteins accumulated to similar levels. Compelling evidence suggests that compromised NMDA receptor-mediated signal transduction is implicated in the pathophysiology of schizophrenia. The NMDA receptor hypofunction hypothesis of schizophrenia arises first from the observation that antagonists of the NMDA receptor, such as phencyclidine and ketamine induced schizophrenia-like psychosis in normal individuals and exacerbated psychotic symptoms in chronic stable patients with schizophrenia. Further evidence comes from studies reporting that combined use of the co-activators of NMDA receptor, such as D-serine, D- alanine, D-cycloserine, or the glycine transporter 1 inhibitor, such as D-sarcosine,MK-2206 with antipsychotic drugs improves the negative symptoms and cognitive deficits in schizophrenia. A double- blind study showed that D-sarcosine alone was effective in reducing both positive and negative symptoms in acute schizo- phrenia patients, especially in drug-na ̈ıve patients, which also supports the involvement of reduced NMDA receptor activity in the pathophysiology of schizophrenia. Several postmortem studies of schizophrenia have reported altered expression of NMDA receptor subunits and their interacting molecules in various brain regions of patients with schizophrenia, indicating that dys-regulated expression of the NMDA receptor and its associated molecules may underlie the pathophysiology of schizophrenia. The post-synaptic density protein 95 is a member of the synapse-associated protein family of scaffolding molecules that control the organization, composition,MK-4827 and function of synapses. The PSD95 plays a critical role in regulating NMDA receptor activity and its signal transduction. It binds to the C- terminal of the NMDA receptor subunits NR2A and 2B, and controls the trafficking, clustering, and anchoring of NMDA receptors at the postsynaptic membrane. The PSD95 is encoded by the DLG4 gene. The Dlg4 knockout mice showed defective synaptic plasticity and impaired spatial learning. Several postmortem studies have revealed altered expression of the PSD95 in various brain regions of patients with schizophrenia. Taken together, these findings indicate that the aberrant expression and function of the PSD95 may contribute to the compromised NMDA receptor-mediated signaling in schizophrenia. Furthermore, the DLG4 gene that encodes the PSD95 was mapped to chromosome 17p13.1, a region linked to schizophrenia. Thus, the DLG4 gene is a reasonable candidate gene of schizophrenia in view of the high genetic basis of the etiology of schizophrenia. However, to our knowledge, no mutations of the DLG4 gene associated with schizophrenia have been identified so far. The study aimed to investigate whether there are genetic variants of the DLG4 that may confer an increased risk to schizophrenia. To test this hypothesis, we re-sequenced the core promoter, all the exons, and the 39 untranslated regions of the DLG4 gene in a sample of Han Taiwanese schizophrenic patients and conducted a case-control association analysis. We also performed reporter gene activity assay to characterize the genetic variants at the 59 and 39ends of the DLG4 gene identified in this study. Schizophrenia is a complex genetic disease with polygenic involvement in its etiology. Currently, two hypotheses have been proposed to account for the genetic basis of schizophrenia.