{"created":"2022-05-06T01:18:14.877185+00:00","id":2000438,"links":{},"metadata":{"_buckets":{"deposit":"a6299dc6-54d9-41eb-b89b-9a503350b05d"},"_deposit":{"id":"2000438","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"2000438"},"status":"published"},"_oai":{"id":"oai:niigata-u.repo.nii.ac.jp:02000438","sets":["453:456","471:537:538:1651799000234"]},"author_link":[],"control_number":"2000438","item_1627361970403":{"attribute_name":"出版タイプ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_7_biblio_info_6":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2021-06","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"4-6","bibliographicPageEnd":"90","bibliographicPageStart":"81","bibliographicVolumeNumber":"135","bibliographic_titles":[{"bibliographic_title":"新潟医学会雑誌","bibliographic_titleLang":"ja"}]}]},"item_7_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"進行性核上性麻痺(progressive supranuclear palsy : PSP)は，神経細胞およびグリア細胞に不溶化したリン酸化タウが蓄積する神経変性疾患である．PSPの大部分は孤発性に発症する多因子性疾患であるが，一部の症例は家族内発症が報告されている．PSPに類似した本邦の家族性タウオパチーに対して全エクソーム解析が行われ，BSN変異が原因となることが報告された．本研究では，PSPとBSNの関連に着目し，PSPと臨床診断された症例を対象にBSNの遺伝子解析を行った．エクソーム解析により3種類のBSNバリアントを同定した．BSN p.P3866Aは既報と同じであり，p.A1710Tとp.T2043Mは新規バリアントであった．これらのBSNバリアントは，公共のデータベースにおけるアレル頻度が0.1％以下と極めて稀な低頻度バリアントであったまた，p.T2043MバリアントのCADDスコアは15.3と高く，PSPとの関連性を支持する所見であった．次に，ヒト型・タウを安定発現したHEK293細胞に野生型および変異型BSNの遺伝子導入を行い，BSNバリアントがタウ不溶性に及ぼす影響を検討した．p.T2043M変異型bassoonを導入すると野生型と比し，サルコシル不溶性タウが約2倍に増加した．一方，p.A1710T, p.P3866A変異型bassoonは，タウ不溶性に及ぼす効果は明かでなかった．タウと同様に，不溶性画分におけるbassoon量を解析したが，野生型と変異型BSNを導入した細胞で有意な差は認めなかった．PSP脳におけるBSN遺伝子発現量を解析する目的で，PSP剖検脳(n=54)と対照脳(n=24)から全RNAを抽出し，RNA-seq解析を行った．PSP脳のBSN発現量は21.0±13.5，対照脳は25.3±10.2であり，PSP脳で低値を示したが有意な差は認めなかった．BSN変異の一部は，タウ不溶性を亢進させ，PSP発症に関与している可能性が考えられた．一方，タウ不溶化には影響を及ぼさないBSN低頻度バリアントも存在し，BSNを介したPSPの病態に多様性があることが示唆された．","subitem_description_language":"ja","subitem_description_type":"Abstract"}]},"item_7_publisher_7":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"新潟医学会","subitem_publisher_language":"ja"}]},"item_7_relation_28":{"attribute_name":"他の資源との関係","attribute_value_mlt":[{"subitem_relation_type":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"https://hdl.handle.net/10191/0002000288","subitem_relation_type_select":"HDL"}}]},"item_7_source_id_11":{"attribute_name":"書誌レコードID","attribute_value_mlt":[{"subitem_source_identifier":"AN00182415","subitem_source_identifier_type":"NCID"}]},"item_7_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0029-0440","subitem_source_identifier_type":"PISSN"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"樋口, 陽","creatorNameLang":"ja"},{"creatorName":"Higuchi, Yo","creatorNameLang":"en"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_access","date":[{"dateType":"Available","dateValue":"2022-05-06"}],"displaytype":"detail","filename":"135(4-6)_81-90.pdf","filesize":[{"value":"6.59MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"objectType":"fulltext","url":"https://niigata-u.repo.nii.ac.jp/record/2000438/files/135(4-6)_81-90.pdf"},"version_id":"5bc0bb4e-8153-4bda-8496-0c56a71b6297"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"進行性核上性麻痺","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"タウ","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"bassoon","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"低頻度バリアント","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"トランスクリプトーム","subitem_subject_language":"ja","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"departmental bulletin paper","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"進行性核上性麻痺におけるBSNバリアントの同定と分子病態機序の解明","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"進行性核上性麻痺におけるBSNバリアントの同定と分子病態機序の解明","subitem_title_language":"ja"},{"subitem_title":"Exploring Molecular Mechanisms by BSN Mutations Identified in Patients with Progressive Supranuclear Palsy","subitem_title_language":"en"}]},"item_type_id":"7","owner":"1","path":["456","1651799000234"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2022-05-06"},"publish_date":"2022-05-06","publish_status":"0","recid":"2000438","relation_version_is_last":true,"title":["進行性核上性麻痺におけるBSNバリアントの同定と分子病態機序の解明"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2022-12-15T04:35:53.191896+00:00"}