Generation and analysis of novel Reln-deleted mouse model corresponding to exonic Reln deletion in schizophrenia

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K07384
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49010:Pathological biochemistry-related
• Research Institution: Nagoya University
• Principal Investigator: MORI DAISUKE 名古屋大学, 脳とこころの研究センター(医), 特任准教授 (00381997)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 統合失調症 / リーリン / モデルマウス

Outline of Final Research Achievements

The phenotype of homozygous Reln-del mice was similar to that of reeler mice with cerebellar atrophy, dysplasia of the cerebral layers, and abrogated protein levels of cerebral reelin. The expression of reelin in heterozygous Reln-del mice was approximately half of that in wild-type mice. Conversely, behavioral analyses in heterozygous Reln-del mice without cerebellar atrophy or dysplasia showed abnormal social novelty in the three-chamber social interaction test. In vitro reaggregation formation and neuronal migration were severely altered in the cerebellar cultures of homozygous Reln-del mice.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

多くの研究により報告されているReln変異マウスの行動変化には、統合失調症に似た表現型が見られた。加えてReln欠失統合失調症患者を同定し、iPS細胞の樹立から神経細胞移動の方向性異常を見出すことができた。Reln欠失マウスとReln欠失iPS細胞の相互解析からリーリン欠失を介した統合失調症の病態メカニズムを明らかにし、創薬につなげる礎となる可能性がある。