{"created":"2023-05-15T14:57:09.646069+00:00","id":77567,"links":{},"metadata":{"_buckets":{"deposit":"b029ed8e-0106-478b-8f29-e9dfcafb0cfe"},"_deposit":{"created_by":1,"id":"77567","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"77567"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00077567","sets":["1"]},"author_link":["1004383","1004378","1004379","1004384","1004386","1004380","1004388","1004389","1004382","1004377","1004381","1004385","1004387"],"item_8_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2019-07","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"34","bibliographicPageEnd":"12765","bibliographicPageStart":"12754","bibliographicVolumeNumber":"294","bibliographic_titles":[{"bibliographic_title":"The Journal of Biological Chemistry"}]}]},"item_8_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"In cortical regions of brains from individuals with preclinical or clinical Alzheimer's disease (AD), extracellular β-amyloid (Aβ) deposition precedes the aggregation of pathological intracellular tau (the product of the gene microtubule-associated protein tau (MAPT)). To our knowledge, current mouse models of tauopathy reconstitute tau pathology by overexpressing mutant human tau protein. Here, through a homologous recombination approach that replaced the entire murine Mapt gene with the human ortholog, we developed knock-in mice with humanized Mapt to create an in vivo platform for studying human tauopathy. Of note, the humanized Mapt expressed all six tau isoforms present in humans. We next cross-bred the MAPT knock-in mice with single amyloid precursor protein (App) knock-in mice to investigate the Aβ–tau axis in AD etiology. The double-knock-in mice exhibited higher tau phosphorylation than did single MAPT knock-in mice but initially lacked apparent tauopathy and neurodegeneration, as observed in the single App knock-in mice. We further observed that tau humanization significantly accelerates cell-to-cell propagation of AD brain-derived pathological tau both in the absence and presence of Aβ-amyloidosis. In the presence of Aβ-amyloidosis, tau accumulation was intensified and closely associated with dystrophic neurites, consistently showing that Aβ-amyloidosis affects tau pathology. Our results also indicated that the pathological human tau interacts better with human tau than with murine tau, suggesting species-specific differences between these orthologous pathogenic proteins. We propose that the MAPT knock-in mice will make it feasible to investigate the behaviors and characteristics of human tau in an animal model.","subitem_description_type":"Abstract"}]},"item_8_relation_13":{"attribute_name":"PubMed番号","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"31273083","subitem_relation_type_select":"PMID"}}]},"item_8_relation_14":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"10.1074/jbc.RA119.009487","subitem_relation_type_select":"DOI"}}]},"item_8_relation_17":{"attribute_name":"関連サイト","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"http://www.jbc.org/content/294/34/12754.long","subitem_relation_type_select":"URI"}}]},"item_8_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0021-9258","subitem_source_identifier_type":"ISSN"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"metadata only access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_14cb"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Saito, Takashi"}],"nameIdentifiers":[{"nameIdentifier":"1004377","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Mihira, Naomi"}],"nameIdentifiers":[{"nameIdentifier":"1004378","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Matsuba, Yukio"}],"nameIdentifiers":[{"nameIdentifier":"1004379","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Sasaguri, Hiroki"}],"nameIdentifiers":[{"nameIdentifier":"1004380","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Hashimoto, Shoko"}],"nameIdentifiers":[{"nameIdentifier":"1004381","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Narasimhan, Sneha"}],"nameIdentifiers":[{"nameIdentifier":"1004382","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Zhang, Bin"}],"nameIdentifiers":[{"nameIdentifier":"1004383","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Murayama, Shigeo"}],"nameIdentifiers":[{"nameIdentifier":"1004384","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Higuchi, Makoto"}],"nameIdentifiers":[{"nameIdentifier":"1004385","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"M. Y. Lee, Virginia"}],"nameIdentifiers":[{"nameIdentifier":"1004386","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Q. Trojanowski, John"}],"nameIdentifiers":[{"nameIdentifier":"1004387","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"C. Saido, Takaomi"}],"nameIdentifiers":[{"nameIdentifier":"1004388","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Makoto, Higuchi","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1004389","nameIdentifierScheme":"WEKO"}]}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"Humanization of the entire murine Mapt gene provides a murine model of pathological human tau propagation","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Humanization of the entire murine Mapt gene provides a murine model of pathological human tau propagation"}]},"item_type_id":"8","owner":"1","path":["1"],"pubdate":{"attribute_name":"公開日","attribute_value":"2019-11-21"},"publish_date":"2019-11-21","publish_status":"0","recid":"77567","relation_version_is_last":true,"title":["Humanization of the entire murine Mapt gene provides a murine model of pathological human tau propagation"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-15T19:27:28.308885+00:00"}