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YAMAGATA Tetsushi

    Specially Appointed Assistant Professor
Last Updated :2025/10/25

Researcher Information

ORCID ID

J-Global ID

Research Areas

  • Life sciences / Molecular biology

Academic & Professional Experience

  • 2020/04 - Today  Institute of Brain Sciences, Nagoya City University Graduate School of Medical SciencesDepartment of Neurodevelopmental Disorder Genetics特任助教
  • 2004/04 - 2020/03  理化学研究所脳神経科学研究センター神経遺伝研究チームチーム研究員
  • 2001/04 - 2003/09  東海大学医学部分子生命科学2特任助手
  • 1998/04 - 2001/03  東海大学医学部分子生命科学2奨励研究員

Published Papers

Conference Activities & Talks

  • Detailed distribution analysis of epilepsy/neurodevelopmental disorder proteins Nav1.1 and Nav1.2  [Not invited]
    山形 哲司; 鈴木 俊光; 日比 悠里名; 荻原郁夫; 山川和弘
    日本人類遺伝学会第68回大会  2023/10
  • ナトリウムチャネルNav1.1の大脳皮質5層錐体路投射細胞 における発現はドラべ症候群における突然死神経回路を明らかにする  [Not invited]
    山川 和弘; 鈴木 俊光; 山形 哲司
    第45回日本神経科学大会 (沖縄)  2022/07
  • Nav1.1分布解析とNav1.1発現量増加によるドラべ症候群遺伝子治療の試み  [Not invited]
    山形 哲司; 山川 和弘
    第54回日本てんかん学会学術集会  2021/09
  • 環状20番染色体症候群の遺伝子研究  [Invited]
    山形 哲司
    第38回 日本てんかん学会学術集会  2004/09

MISC

Awards & Honors

  • 2010/10 日本てんかん学会 優秀ポスター賞
     X染色体には乳児重症ミオクロニーてんかんの遺伝的修飾因子が存在する 
    受賞者: 山形 哲司

Research Grants & Projects

  • 日本学術振興会：科学研究費助成事業
    Date (from‐to) : 2023/04 -2026/03 
    Author : 山形 哲司
     
    電位依存性ナトリウムチャネルα2サブユニット(Nav1.2)をコードするSCN2A遺伝子の変異は、自閉スペクトラム症、知的障害、てんかん、統合失調症など広範囲な神経疾患を引き起こすことが知られている。現時点では、SCN2Aの変異による疾患の発症機序を説明する神経回路は特定されておらず、その機序を理解するためには、SCN2Aを発現する神経とその神経接続を明らかにすることが重要であると考える。本研究は、Scn2a-CreノックインマウスでのCre組み換え酵素(Cre)と蛍光レポーター遺伝子を組み合わせた細胞標識と逆行性色素による標識でNav1.2を発現する神経細胞とそれが構成する神経回路を分析することを目的とする。 本年度は、マウス脳内でScn2aの発現を検出するために作製したScn2a遺伝子の3’-UTRにIRES配列とCre-ERt2遺伝子を組み込んだマウス(Scn2a-IRES-Cre)の評価を行った。Nav1.2発現細胞において、Creが機能することをScn2a-IRES-CreマウスとRosa26遺伝子座にtdTomato蛍光タンパク遺伝子組み込んだマウスを交配して確認した。このマウス脳内ではScn2aと共発現するタモキシフェン誘導型CreによってtdTomato蛍光タンパクでNav1.2発現細胞が標識された。4週齢でCreを作用させたマウスでは、tdTomatoが嗅球、大脳皮質、海馬、線条体の一部の細胞と小脳の顆粒細胞で発現していたが、視床、延髄ではその発現細胞が観察されなかった。この結果において、tdTomato陽性細胞分布は、既知のNav1.2の発現と矛盾しなかったが、、4週齢のScn2a-IRES-Creマウスでは、、Creの組み換え反応によって十分にNav1.2の発現が検出されなかった可能性がある。
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2010 -2011 
    Author : YAMAGATA Tetsushi
     
    As a model mouse for Dravet syndrome, the Nav1.1 deficient mouse(C57BL/6J background) that introduced R1407X mutation in the Scn1a gene has been investigated in our laboratory(Ogiwara et al., J Neurosci 27 : 5903-5914, 2007. Heterozygous mice(Scn1a+/-) exhibit spontaneous seizures, and approximately 60% of them survive to adulthood. Interestingly, this survivability of heterozygous mice depended on mouse strain. The strain dependency of latency of sudden death indicates that genetic background carries dominant modifier alleles at one or more loci that determine the severity of the epilepsy phenotype. In this study, to identify modifier genes, we performed genetic mapping of the sudden death phenotype using backcrossing to MSM/Ms strain. The results show 2 types of modifier genes involve in mortality induced by epilepsy. 1^ modifier gene that is highly sensitive to the sudden death is located on chromosome X. Because backcrossing with MSM/Ms mice increased survival rate in each generation, we estimated that the autosomes of MSM/Ms strain have 2^ modifier gene(s) to resist symptoms of epilepsy also.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2008 -2009 
    Author : YAMAGATA Tetsushi
     
    In this study, to develop gene therapy for severe myoclonic epilepsy in infancy model mice, pegylated immunoliposomes were investigated and improved. Whereas preparation steps of liposomes have been optimized, expression of transgene was not sufficient to apply the therapy to SMEI model mice. However, results of this study will lead to improvement of liposome that provides enough gene expression in the target tissue. Thus the gene therapy for SMEI model mice may be possible in near future.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2006 -2007 
    Author : YAMAKAWA Kazuhiro; YAMAGATA Tetsshi
     
    Severe myoclonic epilepsy in infancy (SMEI) is caused by mutations in the SCN1A gene encoding a voltage-gated sodium channel alpha-subunit type-1, Nav1.1. The mouse with Scnla nonsence mutation (Scnla-KI) that we recently generated and reported (Ogiwara, et. al., J Neurosci 22: 5903-5914, 2007) shows severe epileptic seizures and the homozygote die within 2 weeks. In Scnla-KI mouse, no Nav1.1 protein is detected indicating that haploinsufficiency, rather than dominant-negative effects of truncated Nav1.1 proteins, is the pathological basis for SMEI. We also showed the functional defects specifically in inhibitory neurons and not in excitatory neurons. Furthermore, we found that in wild-type mouse Nev1.1 is localized at axon and somata of a subclass of inhibitory neurons, parvalbumin-positive basket cells. The Scnla-KI with B6 genetic background shows severee phenotypes compared to that wit 129 background. By using MSM mice, we identified the modifier gene locus at X-chromosome, and narrowed the region by usin the consomic mouse developed by Dr. Toshihiko Shiroishi.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2002 -2004 
    Author : INOKO Hidetoshi; KIMURA Minoru; ANDO Asako; YOSHIMURA Shinichi; YAMAMORI Tetsuo
     
    In order to elucidate a role of MHC molecules in the central nervous system (CNS), we have examined the expression of classical and non-classical class I molecules in the CNS of C57BL/6 mice by using RT-PCR and immuno-histochemistry. In class I molecules, although H2-K and H2-D transcripts were found by RT PCR analysis, these proteins were mainly localized in endothelial cells and choroids plexus cells by immuno-histochemical study using an anti-class I antibody. The staining of neuronal cells was faint or weak, and the characteristic distribution of class I MHC molecules was not recognized in neuronal cells. In contrast, non-classical class I proteins were localized mainly in the neuronal cells. The strong staining of H2-Qa 1 protein was observed In the nerve cells localized in the 5th and 6th layer of cerebral cortex, hippocampus and the tuberal nucleus. These data suggested that non-classical MHC class I molecules may have special roles in nerve cells of CNS. It was reported that there are over 10 genes coding the non-classical class I molecules in mouse, however, the exact number or gene structures had not been determined. We estimated the 17 non-classical class I genes from the draft sequence of mouse genome by computerr analysis, and RT-PCR analysis was performed on total RNAs extracted from cerebral cortex, hypothalamus, cerebellum, thymus, small intestine, liver, kidney and spleen. Eight non-classical MHC class I transcripts were observed in cerebral cortex, hypothalamus and cerebellum, although the seven among eight genes were expressed in all the tissues so far examined. The H2-M5 gene is expressed specifically for CNS. The expression of eight non-classical MHC class I molecules may suggest an important role of these molecules in the remodeling and plasticity of connection of nerve cells or in some immune responses in the CNS. To determine exact roles of non-classical MHC class I molecules, the production of the H2-M5 gene targeting mouse and the H2-Qa1 overexpressing mouse are now in progress.

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