{"_buckets": {"deposit": "a880a954-6813-49eb-9b1f-b3c4b2e478de"}, "_deposit": {"id": "20454", "owners": [], "pid": {"revision_id": 0, "type": "depid", "value": "20454"}, "status": "published"}, "_oai": {"id": "oai:soar-ir.repo.nii.ac.jp:00020454", "sets": ["1016:1017"]}, "author_link": ["107370", "107371", "107372", "107373", "107374", "107375", "107376", "107377", "107378", "107379", "107380", "107381", "107382", "107383", "107384", "107385", "107386", "107387", "107388", "107389", "107390", "107391", "107392", "107393", "107394", "107395", "107396"], "item_1628147817048": {"attribute_name": "\u51fa\u7248\u30bf\u30a4\u30d7", "attribute_value_mlt": [{"subitem_version_resource": "http://purl.org/coar/version/c_970fb48d4fbd8a85", "subitem_version_type": "VoR"}]}, "item_6_biblio_info_6": {"attribute_name": "\u66f8\u8a8c\u60c5\u5831", "attribute_value_mlt": [{"bibliographicIssueDates": {"bibliographicIssueDate": "2017-03-28", "bibliographicIssueDateType": "Issued"}, "bibliographicIssueNumber": "2", "bibliographicPageStart": "e0250", "bibliographicVolumeNumber": "4", "bibliographic_titles": [{"bibliographic_title": "eNeuro"}]}]}, "item_6_description_20": {"attribute_name": "\u6284\u9332", "attribute_value_mlt": [{"subitem_description": "Age-associated neurodegenerative diseases, such as Alzheimer\u2019s disease, Parkinson\u2019s disease, and the polyglutamine (polyQ) diseases, are becoming prevalent as a consequence of elongation of the human lifespan. Although various rodent models have been developed to study and overcome these diseases, they have limitations in their translational research utility owing to differences from humans in brain structure and function and in drug metabolism. Here, we generated a transgenic marmoset model of the polyQ diseases, showing progressive neurological symptoms including motor impairment. Seven transgenic marmosets were produced by lentiviral introduction of the human ataxin 3 gene with 120 CAG repeats encoding an expanded polyQ stretch. Although all offspring showed no neurological symptoms at birth, three marmosets with higher transgene expression developed neurological symptoms of varying degrees at 3\u20134 months after birth, followed by gradual decreases in body weight gain, spontaneous activity, and grip strength, indicating time-dependent disease progression. Pathological examinations revealed neurodegeneration and intranuclear polyQ protein inclusions accompanied by gliosis, which recapitulate the neuropathological features of polyQ disease patients. Consistent with neuronal loss in the cerebellum, brain MRI analyses in one living symptomatic marmoset detected enlargement of the fourth ventricle, which suggests cerebellar atrophy. Notably, successful germline transgene transmission was confirmed in the second-generation offspring derived from the symptomatic transgenic marmoset gamete. Because the accumulation of abnormal proteins is a shared pathomechanism among various neurodegenerative diseases, we suggest that this new marmoset model will contribute toward elucidating the pathomechanisms of and developing clinically applicable therapies for neurodegenerative diseases.", "subitem_description_type": "Abstract"}]}, "item_6_description_30": {"attribute_name": "\u8cc7\u6e90\u30bf\u30a4\u30d7\uff08\u30b3\u30f3\u30c6\u30f3\u30c4\u306e\u7a2e\u985e\uff09", "attribute_value_mlt": [{"subitem_description": "Article", "subitem_description_type": "Other"}]}, "item_6_description_5": {"attribute_name": "\u5f15\u7528", "attribute_value_mlt": [{"subitem_description": "eNeuro.4(2):e0250(2017)", "subitem_description_type": "Other"}]}, "item_6_link_3": {"attribute_name": "\u4fe1\u5dde\u5927\u5b66\u7814\u7a76\u8005\u7dcf\u89a7\u3078\u306e\u30ea\u30f3\u30af", "attribute_value_mlt": [{"subitem_link_text": "Tomioka, Ikuo", "subitem_link_url": "http://soar-rd.shinshu-u.ac.jp/profile/ja.WNAhPUkh.html"}]}, "item_6_link_67": {"attribute_name": "WoS", "attribute_value_mlt": [{"subitem_link_text": "Web of Science", "subitem_link_url": "http://gateway.isiknowledge.com/gateway/Gateway.cgi?\u0026GWVersion=2\u0026SrcAuth=ShinshuUniv\u0026SrcApp=ShinshuUniv\u0026DestLinkType=FullRecord\u0026DestApp=WOS\u0026KeyUT=000397567900013"}]}, "item_6_publisher_4": {"attribute_name": "\u51fa\u7248\u8005", "attribute_value_mlt": [{"subitem_publisher": "Society for Neuroscience"}]}, "item_6_relation_47": {"attribute_name": "PubMed", "attribute_value_mlt": [{"subitem_relation_name": [{"subitem_relation_name_text": "28374014"}], "subitem_relation_type_id": {"subitem_relation_type_id_text": "https://www.ncbi.nlm.nih.gov/pubmed/28374014", "subitem_relation_type_select": "PMID"}}]}, "item_6_relation_48": {"attribute_name": "DOI", "attribute_value_mlt": [{"subitem_relation_name": [{"subitem_relation_name_text": "10.1523/ENEURO.0250-16.2017"}], "subitem_relation_type_id": {"subitem_relation_type_id_text": "https://doi.org/10.1523/ENEURO.0250-16.2017", "subitem_relation_type_select": "DOI"}}]}, "item_6_rights_62": {"attribute_name": "\u6a29\u5229", "attribute_value_mlt": [{"subitem_rights": "Copyright \u00a9 2017 Tomioka et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed."}]}, "item_6_select_64": {"attribute_name": "\u8457\u8005\u7248\u30d5\u30e9\u30b0", "attribute_value_mlt": [{"subitem_select_item": "publisher"}]}, "item_6_source_id_35": {"attribute_name": "ISSN", "attribute_value_mlt": [{"subitem_source_identifier": "2373-2822", "subitem_source_identifier_type": "ISSN"}]}, "item_6_source_id_39": {"attribute_name": "NII ISSN", "attribute_value_mlt": [{"subitem_source_identifier": "2373-2822", "subitem_source_identifier_type": "ISSN"}]}, "item_6_text_69": {"attribute_name": "wosonly authkey", "attribute_value_mlt": [{"subitem_text_value": "Neurodegenerative disease; Polyglutamine disease; Transgenic monkey; Common marmoset"}]}, "item_6_text_70": {"attribute_name": "wosonly keywords", "attribute_value_mlt": [{"subitem_text_value": "SPINOCEREBELLAR ATAXIA TYPE-3; MARMOSET CALLITHRIX-JACCHUS; MODERATE ALZHEIMERS-DISEASE; MACHADO-JOSEPH-DISEASE; COMMON MARMOSET; NEURODEGENERATIVE DISEASES; HUNTINGTONS-DISEASE; GERMLINE TRANSMISSION; NONHUMAN PRIMATE; MOUSE MODEL"}]}, "item_6_textarea_68": {"attribute_name": "wosonly abstract", "attribute_value_mlt": [{"subitem_textarea_value": "Age-associated neurodegenerative diseases, such as Alzheimer\u0027s disease, Parkinson\u0027s disease, and the polyglutamine (polyQ) diseases, are becoming prevalent as a consequence of elongation of the human lifespan. Although various rodent models have been developed to study and overcome these diseases, they have limitations in their translational research utility owing to differences from humans in brain structure and function and in drug metabolism. Here, we generated a transgenic marmoset model of the polyQ diseases, showing progressive neurological symptoms including motor impairment. Seven transgenic marmosets were produced by lentiviral introduction of the human ataxin 3 gene with 120 CAG repeats encoding an expanded polyQ stretch. Although all offspring showed no neurological symptoms at birth, three marmosets with higher transgene expression developed neurological symptoms of varying degrees at 3-4 months after birth, followed by gradual decreases in body weight gain, spontaneous activity, and grip strength, indicating time-dependent disease progression. Pathological examinations revealed neurodegeneration and intranuclear polyQ protein inclusions accompanied by gliosis, which recapitulate the neuropathological features of polyQ disease patients. Consistent with neuronal loss in the cerebellum, brain MRI analyses in one living symptomatic marmoset detected enlargement of the fourth ventricle, which suggests cerebellar atrophy. Notably, successful germline transgene transmission was confirmed in the second-generation offspring derived from the symptomatic transgenic marmoset gamete. Because the accumulation of abnormal proteins is a shared pathomechanism among various neurodegenerative diseases, we suggest that this new marmoset model will contribute toward elucidating the pathomechanisms of and developing clinically applicable therapies for neurodegenerative diseases."}]}, "item_creator": {"attribute_name": "\u8457\u8005", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "Tomioka, Ikuo"}], "nameIdentifiers": [{"nameIdentifier": "107370", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Ishibashi, Hidetoshi"}], "nameIdentifiers": [{"nameIdentifier": "107371", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Minakawa, Eiko N."}], "nameIdentifiers": [{"nameIdentifier": "107372", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Motohashi, Hideyuki H."}], "nameIdentifiers": [{"nameIdentifier": "107373", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Takayama, Osamu"}], "nameIdentifiers": [{"nameIdentifier": "107374", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Saito, Yuko"}], "nameIdentifiers": [{"nameIdentifier": "107375", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Popiel, H. 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