{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T01:03:17Z","timestamp":1787965397654,"version":"build-2784847793"},"reference-count":32,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,9,12]],"date-time":"2022-09-12T00:00:00Z","timestamp":1662940800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["202300410259"],"award-info":[{"award-number":["202300410259"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017699","name":"Henan Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["202001043"],"award-info":[{"award-number":["202001043"]}],"id":[{"id":"10.13039\/501100017699","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006407","name":"Natural Science Foundation of Henan Province","doi-asserted-by":"publisher","award":["2021T140184"],"award-info":[{"award-number":["2021T140184"]}],"id":[{"id":"10.13039\/501100006407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Anim Models and Exp Med"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>SHARPIN (SHANK\u2010associated RH domain interactor) is a component of the linear ubiquitination complex that regulates the NF\u2010\u03baB signaling pathway. To better understand the function of SHARPIN, we sought to establish a novel genetically engineered Syrian hamster with SHARPIN disruption using the CRISPR\/Cas9 system.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A single\u2010guide ribonucleic acid targeting exon 1 of SHARPIN gene was designed and constructed. The zygotes generated by cytoplasmic injection of the Cas9\/gRNA ribonucleoprotein were transferred into pseudopregnant hamsters. Neonatal mutants were identified by genotyping. SHARPIN protein expression was detected using Western blotting assay. Splenic, mesenteric lymph nodes (MLNs), and thymic weights were measured, and organ coefficients were calculated. Histopathological examination of the spleen, liver, lung, small intestine, and esophagus was performed independently by a pathologist. The expression of lymphocytic markers and cytokines was evaluated using reverse transcriptase\u2010quantitative polymerase chain reaction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All the offspring harbored germline\u2010transmitted SHARPIN mutations. Compared with wild\u2010type hamsters, SHARPIN protein was undetectable in SHARPIN<jats:sup>\u2212\/\u2212<\/jats:sup> hamsters. Spleen enlargement and splenic coefficient elevation were spotted in SHARPIN<jats:sup>\u2212\/\u2212<\/jats:sup> hamsters, with the descent of MLNs and thymuses. Further, eosinophil infiltration and structural alteration in spleens, livers, lungs, small intestines, and esophagi were obvious after the deletion of SHARPIN. Notably, the expression of CD94 and CD22 was downregulated in the spleens of knockout (KO) animals. Nonetheless, the expression of CCR3, CCL11, <jats:italic>Il4<\/jats:italic>, and <jats:italic>Il13<\/jats:italic> was upregulated in the esophagi. The expression of NF\u2010\u03baB and phosphorylation of NF\u2010\u03baB and I\u03baB protein significantly diminished in SHARPIN<jats:sup>\u2212\/\u2212<\/jats:sup> animals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>A novel SHARPIN KO hamster was successfully established using the CRISPR\/Cas9 system. Abnormal development of secondary lymphoid organs and eosinophil infiltration in multiple organs reveal its potential in delineating SHARPIN function and chronic inflammation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ame2.12265","type":"journal-article","created":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T06:50:45Z","timestamp":1663051845000},"page":"489-498","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Characterization of <scp>SHARPIN<\/scp> knockout Syrian hamsters developed using <scp>CRISPR<\/scp>\/Cas9 system"],"prefix":"10.1002","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1688-3066","authenticated-orcid":false,"given":"Jinxin","family":"Miao","sequence":"first","affiliation":[{"name":"Academy of Chinese Medicine Science Henan University of Chinese Medicine  Zhengzhou Henan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianfeng","family":"Lan","sequence":"additional","affiliation":[{"name":"Sino\u2010British Research Center for Molecular Oncology, National Center for the International Research in Cell and Gene Therapy, School of Basic Sciences, Academy of Medical Sciences Zhengzhou University  Zhengzhou Henan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoran","family":"Guo","sequence":"additional","affiliation":[{"name":"Sino\u2010British Research Center for Molecular Oncology, National Center for the International Research in Cell and Gene Therapy, School of Basic Sciences, Academy of Medical Sciences Zhengzhou University  Zhengzhou Henan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianyao","family":"Wang","sequence":"additional","affiliation":[{"name":"Sino\u2010British Research Center for Molecular Oncology, National Center for the International Research in Cell and Gene Therapy, School of Basic Sciences, Academy of Medical Sciences Zhengzhou University  Zhengzhou Henan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangtao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oncology, Longhua Hospital Shanghai University of Traditional Chinese Medicine  Shanghai People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Academy of Chinese Medicine Science Henan University of Chinese Medicine  Zhengzhou Henan People's Republic of China"},{"name":"Sino\u2010British Research Center for Molecular Oncology, National Center for the International Research in Cell and Gene Therapy, School of Basic Sciences, Academy of Medical Sciences Zhengzhou University  Zhengzhou Henan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panpan","family":"Yang","sequence":"additional","affiliation":[{"name":"Sino\u2010British Research Center for Molecular Oncology, National Center for the International Research in Cell and Gene Therapy, School of Basic Sciences, Academy of Medical Sciences Zhengzhou University  Zhengzhou Henan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoze","family":"Li","sequence":"additional","affiliation":[{"name":"Sino\u2010British Research Center for Molecular Oncology, National Center for the International Research in Cell and Gene Therapy, School of Basic Sciences, Academy of Medical Sciences Zhengzhou University  Zhengzhou Henan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery The First Affiliated Hospital of Zhengzhou University  Zhengzhou Henan People's Republic of China"},{"name":"Department of General Thoracic Surgery Hami Central Hospital  Hami Xinjiang People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaohe","family":"Wang","sequence":"additional","affiliation":[{"name":"Sino\u2010British Research Center for Molecular Oncology, National Center for the International Research in Cell and Gene Therapy, School of Basic Sciences, Academy of Medical Sciences Zhengzhou University  Zhengzhou Henan People's Republic of China"},{"name":"Centre for Molecular Oncology Barts Cancer Institute, Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu\u2010Min","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and Department of Otolaryngology New York Medical College and School of Medicine  Valhalla New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingsan","family":"Miao","sequence":"additional","affiliation":[{"name":"Academy of Chinese Medicine Science Henan University of Chinese Medicine  Zhengzhou Henan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,9,12]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-020-01023-w"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1006\/mcne.2000.0940"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2012.01574.x"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09814"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09815"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-021-01680-5"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200103)31:3<734::AID-IMMU734>3.0.CO;2-9"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gene.6364403"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2001602118"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/rmb2.12241"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02329"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/pim.12768"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006833"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0109755"},{"key":"e_1_2_10_16_1","first-page":"56263","article-title":"Production of genetically engineered Golden Syrian hamsters by pronuclear injection of the CRISPR\/Cas9 complex","volume":"131","author":"Li R","year":"2018","journal-title":"J Vis Exp"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/v10050243"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v26.i32.4802"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.4103\/jcar.jcar_18_21"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04441-6"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.044602"},{"issue":"10","key":"e_1_2_10_22_1","first-page":"1127","article-title":"Validation of stable housekeeping genes for quantitative real time PCR in Golden Syrian hamster","volume":"55","author":"Miao J\u2010X","year":"2021","journal-title":"Indian J Anim Res"},{"issue":"3","key":"e_1_2_10_23_1","first-page":"972","article-title":"A spontaneous mutation characterized by chronic proliferative dermatitis in C57BL mice","volume":"143","author":"Hogenesch H","year":"1993","journal-title":"Am J Pathol"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2787-6"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-3497"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.09.014"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.01.035"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2017.03.005"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2019.104696"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0085666"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2015.08.012"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1517\/17460441.2014.897324"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.13466"}],"container-title":["Animal Models and Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ame2.12265","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ame2.12265","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ame2.12265","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T10:52:09Z","timestamp":1698663129000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ame2.12265"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,12]]},"references-count":32,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2023,10]]}},"alternative-id":["10.1002\/ame2.12265"],"URL":"https:\/\/doi.org\/10.1002\/ame2.12265","archive":["Portico"],"relation":{},"ISSN":["2576-2095","2576-2095"],"issn-type":[{"value":"2576-2095","type":"print"},{"value":"2576-2095","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,12]]},"assertion":[{"value":"2022-04-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}