{"_buckets": {"deposit": "637325d3-3ed8-4d42-9760-9ca392f957fa"}, "_deposit": {"created_by": 1, "id": "1002", "owners": [1], "pid": {"revision_id": 0, "type": "depid", "value": "1002"}, "status": "published"}, "_oai": {"id": "oai:ir.soken.ac.jp:00001002", "sets": ["20"]}, "author_link": ["10142", "10141", "10140"], "item_1_biblio_info_21": {"attribute_name": "書誌情報（ソート用）", "attribute_value_mlt": [{"bibliographicIssueDates": {"bibliographicIssueDate": "2004-09-30", "bibliographicIssueDateType": "Issued"}, "bibliographic_titles": [{}]}]}, "item_1_creator_2": {"attribute_name": "著者名", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "田中, 成和"}], "nameIdentifiers": [{"nameIdentifier": "10140", "nameIdentifierScheme": "WEKO"}]}]}, "item_1_creator_3": {"attribute_name": "フリガナ", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "タナカ, シゲカズ"}], "nameIdentifiers": [{"nameIdentifier": "10141", "nameIdentifierScheme": "WEKO"}]}]}, "item_1_date_granted_11": {"attribute_name": "学位授与年月日", "attribute_value_mlt": [{"subitem_dategranted": "2004-09-30"}]}, "item_1_degree_grantor_5": {"attribute_name": "学位授与機関", "attribute_value_mlt": [{"subitem_degreegrantor": [{"subitem_degreegrantor_name": "総合研究大学院大学"}]}]}, "item_1_degree_name_6": {"attribute_name": "学位名", "attribute_value_mlt": [{"subitem_degreename": "博士（理学）"}]}, "item_1_description_1": {"attribute_name": "ID", "attribute_value_mlt": [{"subitem_description": "2004517", "subitem_description_type": "Other"}]}, "item_1_description_12": {"attribute_name": "要旨", "attribute_value_mlt": [{"subitem_description": "　　Two dominant mouse skin mutants, Recombinant-induced mutation 3 (Rim3) and Rex denuded (Re\u003cSUP\u003eden\u003c/SUP\u003e), arose spontaneously in different inbred strains, but exhibit very similar phenotype of hyperkeratosis and alopecia. Both mutants have a genetic alteration in GasderminA-3 (GsdmA-3), which is a member of novel gene family, Gsdm. The Gsdm family commonly share unique leucine-rich C-terminus domain, but the functions of GsdmA-3 and Gsdm family are largely unknown.\u003cbr /\u003e　　In this study, to elucidate the function of GsdmA-3 in the epidermal morphogenesis, I conducted analysis of spatiotemporal expression patterns of GsdmA-3 and the related genes. In addition, I carried out in-depth characterization of the Rim3 phenotype. The results indicated that GsdmA-3 is specifically expressed in differentiated keratinocytes in epidermis after postnatal stage, but not in proliferating epidermal cells. Immunohistochemical analysis of BrdU-labeled epidermis revealed hyperproliferation and misdifferentiation of the upper follicular cells and the epidermis in the Rim3 mutant. All the results suggested that GsdmA-3 is involved in downregulation of cellproliferation and differentiation of the epidermal stem cells.\u003cbr /\u003eAs collaboration with a research group of National Cancer Institute, Tokyo, it was demonstrated that a human homologue GSDMA has a tumor suppressor activity. Mice heterozygous for Trp53 knockout (Trp53\u003cSUP\u003e-\u003c/SUP\u003e) allele are known to frequently develop lymphomas, but never develop skin tumors. Although mice heterozygous for the Rim3 mutation alone develop no skin tumors, I examined whether GsdmA-3 is involved in tumor suppression in the Trp53\u003cSUP\u003e-\u003c/SUP\u003e genetic background.\u003cbr /\u003eTo do this, I generated mice heterozygous for both of the Rim3 and Trp53\u003cSUP\u003e-\u003c/SUP\u003e alleles. As a result, the double heterozygous mice (GsdmA-3\u003cSUP\u003eRim3\u003c/SUP\u003e/+; Trp53\u003cSUP\u003e+\u003c/SUP\u003e/+) developed multiple metastatic squamous cell carcinomas (SCC) as early as 7 months of the age. In conjunction with the data that a human homologue GSDMA is a tumor suppressor for gastric cancer in human, this result suggested that GsdmA-3 has a function to prevent tumor development in the mouse skin as well.", "subitem_description_type": "Other"}]}, "item_1_description_18": {"attribute_name": "フォーマット", "attribute_value_mlt": [{"subitem_description": "application/pdf", "subitem_description_type": "Other"}]}, "item_1_description_7": {"attribute_name": "学位記番号", "attribute_value_mlt": [{"subitem_description": "総研大甲第808号", "subitem_description_type": "Other"}]}, "item_1_select_14": {"attribute_name": "所蔵", "attribute_value_mlt": [{"subitem_select_item": "有"}]}, "item_1_select_8": {"attribute_name": "研究科", "attribute_value_mlt": [{"subitem_select_item": "生命科学研究科"}]}, "item_1_select_9": {"attribute_name": "専攻", "attribute_value_mlt": [{"subitem_select_item": "18 遺伝学専攻"}]}, "item_1_text_10": {"attribute_name": "学位授与年度", "attribute_value_mlt": [{"subitem_text_value": "2004"}]}, "item_1_text_20": {"attribute_name": "業務メモ", "attribute_value_mlt": [{"subitem_text_value": "（2018年2月20日）本籍など個人情報の記載がある旧要旨・審査要旨を個人情報のない新しいものに差し替えた。承諾書等未確認。要確認該当項目修正のこと。"}]}, "item_creator": {"attribute_name": "著者", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "TANAKA, Shigekazu", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "10142", "nameIdentifierScheme": "WEKO"}]}]}, "item_files": {"attribute_name": "ファイル情報", "attribute_type": "file", "attribute_value_mlt": [{"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2016-02-17"}], "displaytype": "simple", "download_preview_message": "", "file_order": 0, "filename": "甲808_要旨.pdf", "filesize": [{"value": "205.3 kB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_11", "mimetype": "application/pdf", "size": 205300.0, "url": {"label": "要旨・審査要旨 / Abstract, Screening Result", "url": "https://ir.soken.ac.jp/record/1002/files/甲808_要旨.pdf"}, "version_id": "d1f6044d-d03b-4bf6-8f7c-b647532ffaf8"}, {"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2016-02-17"}], "displaytype": "simple", "download_preview_message": "", "file_order": 1, "filename": "甲808_本文.pdf", "filesize": [{"value": "3.6 MB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_11", "mimetype": "application/pdf", "size": 3600000.0, "url": {"label": "本文", "url": "https://ir.soken.ac.jp/record/1002/files/甲808_本文.pdf"}, "version_id": "3cfddf70-671e-47af-87de-5c023fd27870"}]}, "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": "thesis", "resourceuri": "http://purl.org/coar/resource_type/c_46ec"}]}, "item_title": "Functional analysis of Rim3 mutation that exhibits aberrant epidermal morphogenesis.", "item_titles": {"attribute_name": "タイトル", "attribute_value_mlt": [{"subitem_title": "Functional analysis of Rim3 mutation that exhibits aberrant epidermal morphogenesis."}, {"subitem_title": "Functional analysis of Rim3 mutation that exhibits aberrant epidermal morphogenesis.", "subitem_title_language": "en"}]}, "item_type_id": "1", "owner": "1", "path": ["20"], "permalink_uri": "https://ir.soken.ac.jp/records/1002", "pubdate": {"attribute_name": "公開日", "attribute_value": "2010-02-22"}, "publish_date": "2010-02-22", "publish_status": "0", "recid": "1002", "relation": {}, "relation_version_is_last": true, "title": ["Functional analysis of Rim3 mutation that exhibits aberrant epidermal morphogenesis."], "weko_shared_id": 1}