Transmembrane AMPA Receptor Regulatory Protein γ-8 is Associated with Antisocial Personality Disorder
Transmembrane AMPA Receptor Regulatory Protein γ-8 is Associated with Antisocial Personality Disorder作者机构：State Key Laboratory of Pharmaceutical BiotechnologyDepartment of NeurologyDrum Tower HospitalMedical School MOE Key Laboratory of Model Animal for Disease StudyModel Animal Research CenterNanjing University Department of Medical PsychologyNanjing Medical University affiliated Nanjing Brain Hospital Institute for Brain SciencesNanjing University
出 版 物：《神经药理学报》 (Acta Neuropharmacologica)
年 卷 期：2019年第4期
页 面：31-32页
学科分类：1002[医学-临床医学] 100205[医学-精神病与精神卫生学] 10[医学]
主 题：TARP γ-8 SNP G-quadruplex ASPD aggression
摘 要：Antisocial personality disorder( ASPD),a common subtype of personality disorder characterized by irresponsible behavior often leading to criminal behavior,has heritability. In current study,we found SNP rs10420324 in the 1 st intron of CACNG8,the gene encoding transmembrane AMPA receptor regulatory protein γ-8( TARP γ-8),is associated with ASPD in a male prisoner sample in Chinese Han people. The distribution of rs10420324 G is significantly higher in ASPD subjects relative to the normal healthy males. Using a reportermolecule in which the sequence covering rs10420324 were fused to the N-terminal of GFP protein,we found the expression level of the reporting GFP protein,mRNA and pre-mRNA relied on the rs10420324 variants. Furthermore,in 120 fore-cortical brain samples from a Chinese Han brain library,the expression level of TARP γ-8 was associated with the SNP rs10420324. The SNP is located in a guanine-rich region. We found it modulated the conformation and stability of a local G-quadruplex DNA structure,which appeared to regulate the transcription of TARP γ-8. Using TARP γ-8 knockout mice,we found that the decrease of TARP γ-8 lead to abnormal social behaviors and aggression. Therefore,the AMPA receptor auxiliary subunit TARP γ-8 contributes to a risk factor for ASPD.
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