Functional analysis of DISC1 using Disc1-knockout mouse

2014 Fiscal Year Final Research Report

• Project/Area Number: 24700377
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Nagoya University
• Principal Investigator: TSUBOI Daisuke 名古屋大学, 医学(系)研究科(研究院), 特任助教 (80584672)
• Co-Investigator(Renkei-kenkyūsha): KAIBUCHI Kozo 名古屋大学, 大学院医学系研究科, 教授 (00169377)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 統合失調症 / 神経科学 / シナプス可塑性

Outline of Final Research Achievements

Schizophrenia is a devastating psychiatric disorder affecting 1% of the population worldwide. The DISC1 gene locus was originally identified at the breakpoint of a balanced (1;11) (q42;q14) chromosome translocation that co-segregates with schizophrenia, bipolar disorder, and recurrent major depression in a large Scottish family. Therefore, DISC1 gene is a promising susceptibility factor for schizophrenia. In the present study, using a proteomic analysis, I identified RNA-binding proteins including HZF as novel DISC1-interactors. HZF is a component of the RNA granules with inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) mRNA, which acts as a key regulator for synaptic plasticity. DISC1 co-localized with HZF and ITPR1 mRNA in hippocampal dendrites. Furthermore, DISC1 directly associated with several mRNAs including that of ITPR1. The impairment of DISC1 function prohibited the dendritic transport of ITPR1 mRNA and caused altered synaptic plasticity

Free Research Field

神経科学