2023 Fiscal Year Final Research Report
Analyses for the new function of the neuropathy target esterase using genetically engineered mice.
| Project/Area Number |
21K06847
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 48040:Medical biochemistry-related
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| Research Institution | Tokai University |
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Principal Investigator |
Kimura Minoru 東海大学, 医学部, 客員教授 (10146706)
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| Co-Investigator(Kenkyū-buntansha) |
畑中 朋美 城西大学, 薬学部, 教授 (10198749)
赤塚 尚子 東海大学, 医学部, 特定研究員 (20826317)
坂部 貢 千葉大学, 予防医学センター, 特任教授 (70162302)
加藤 明 東海大学, 医学部, 准教授 (70546746)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | 神経障害エステラーゼ / Transgenic Mice / Gene Knockout Mice / Brain Function / Behavior / Organophophate / lipid metabolism / PNPLA6 |
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| Outline of Final Research Achievements |
Neuropathy target esterase (NTE) is a type of lysophospholipase whose amino acid sequence is well conserved across species, and mutations in its gene, PNPLA6, are found in the human motor function diseases. In addition, NTE covalently binds to organophosphorus and causes a variety of neurological symptoms with chemical changes of the complex. As a clue to the pathogenesis of these diseases, we generated six strains of mice with partial mutations in the vicinity of the active center of the NTE and conducted phenotypic analysis focusing on brain function in some of the strains. In our strains we examined, no homozygous mutant mice were born, suggesting that, as in the case of the large deletion knockout mice, a reduced normal NTE activity or a partially mutated NTE itself caused the early developmental abnormalities that resulted in embryonic lethality. Behavioral analysis of some lines of heterozygous partial NTE mutant mice showed reduced function in Rotarod and Open field tests.
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| Free Research Field |
分子生物学
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| Academic Significance and Societal Importance of the Research Achievements |
遺伝子名にあるPatatinはジャガイモなどの貯蔵タンパク質であり、脂肪酸を分解するリパーゼの活性を持つ。PNPLA群の遺伝子は複数種知られ、真核生物から原核生物にまで保存されている。脂質代謝酵素の発現量や分子の一部の変化によって個体の生存までが影響され、脳神経系の機能に影響を及ぼす可能性も示せたことは分子生物学あるいは生物進化学の上で極めて重要な発見と考える。また同様の変異をもつヒト疾患や有機リンの結合によって生じる種々の神経症状に対する発症機構を考え、同時に今後の治療法を探索するためのヒト疾患モデルマウスを提供できる成果を挙げられたことは社会的貢献度の高い成果となったと自負する。
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