Analysis of the influence of autism spectrum disorder related gene mutations on synaptic function and endoplasmic reticulum stress

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K19628
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Jichi Medical University
• Principal Investigator: Kojima Karin 自治医科大学, 医学部, 講師 (00468331)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 自閉症スペクトラム障害 / 小胞体ストレス / ER stress / CADM1 / ノックインマウス / シナプスバランス

Outline of Final Research Achievements

The onset of autism spectrum disorder(ASD) caused by a mutation of the ASD related genes, was considered to be involved in not only loss of function of mutant protein but also gain of function induced by mutant protein. As a common pathology, we assumed an endoplasmic reticulum (ER) stress induction and imbalance of synaptic function by mutation.
As an analysis of the influence of ASD related genes including CADM1 on ER stress, expression of ER stress markers was analyzed after ER stress induction with reagents in patients with mutations and patient families lymphoblasts. Lymphoblasts with mutations were found to be highly susceptible to ER stress. In CADM1 mutation knock-in mice cerebellum, identifying the inhibitory-excitatory synaptic balance is unbalanced, it was suggested the association between mutations and synaptic balance.

Free Research Field

小児神経学