{"created":"2024-12-12T09:12:16.387408+00:00","id":2010719,"links":{},"metadata":{"_buckets":{"deposit":"e016750a-5b32-40d8-b3fb-aed47d038f23"},"_deposit":{"created_by":7,"id":"2010719","owners":[7],"pid":{"revision_id":0,"type":"depid","value":"2010719"},"status":"published"},"_oai":{"id":"oai:tokushima-u.repo.nii.ac.jp:02010719","sets":["1713853213384:1713853295607"]},"author_link":["508","511","1679","1658"],"control_number":"2010719","item_10001_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2022-12-17","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"24","bibliographicPageStart":"16089","bibliographicVolumeNumber":"23","bibliographic_titles":[{"bibliographic_title":"International Journal of Molecular Sciences","bibliographic_titleLang":"en"}]}]},"item_10001_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Mitochondrial ATP production plays an important role in most cellular activities, including growth and differentiation. Previously we reported that Adenylate kinase 2 (AK2) is the main ADP supplier in the mitochondrial intermembrane space in hematopoietic cells, especially in the bone marrow. AK2 is crucial for the production of neutrophils and T cells, and its deficiency causes reticular dysgenesis. However, the relationship between ADP supply by AK2 and neutrophil differentiation remains unclear. In this study, we used CRISPR/Cas9 technology to establish two heterozygous AK2 knock-out HL-60 clones as models for reticular dysgenesis. Their AK2 activities were about half that in the wild-type (WT). Furthermore, neutrophil differentiation was impaired in one of the clones. In silico analysis predicted that the obtained mutations might cause a structural change in AK2. Time course microarray analysis of the WT and mutants revealed that similar gene clusters responded to all-trans retinoic acid treatment, but their expression was lower in the mutants than in WT. Application of fructose partially restored neutrophil differentiation in the heterozygous knock-out HL-60 clone after all-trans retinoic acid treatment. Collectively, our study suggests that the mutation of N-terminal region in AK2 might play a role in AK2-dependent neutrophil differentiation and fructose could be used to treat AK2 deficiency.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_10001_publisher_8":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"MDPI","subitem_publisher_language":"en"}]},"item_10001_rights_15":{"attribute_name":"権利情報","attribute_value_mlt":[{"subitem_rights":"This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).","subitem_rights_language":"en"}]},"item_10001_source_id_9":{"attribute_name":"収録物ID","attribute_value_mlt":[{"subitem_source_identifier":"14220067","subitem_source_identifier_type":"ISSN"}]},"item_10001_version_type_20":{"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_1715043197608":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open 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2","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"mitochondria","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"neutrophil differentiation","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"reticular dysgenesis","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"CRISPR/Cas9","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"fructose","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"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":"The Effect of Heterozygous Mutation of Adenylate Kinase 2 Gene on Neutrophil 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