{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T13:33:14Z","timestamp":1784640794987,"version":"3.55.0"},"reference-count":85,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T00:00:00Z","timestamp":1762300800000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017618","name":"Division of Diabetes, Endocrinology, and Metabolic Diseases","doi-asserted-by":"publisher","award":["DK123264"],"award-info":[{"award-number":["DK123264"]}],"id":[{"id":"10.13039\/100017618","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008519","name":"University of Arkansas for Medical Sciences","doi-asserted-by":"publisher","award":["17\u2010DN\u201008"],"award-info":[{"award-number":["17\u2010DN\u201008"]}],"id":[{"id":"10.13039\/100008519","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Physiological Reports"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Ischemia\u2010reperfusion injury (IRI) is the central contributing factor to acute kidney injury (AKI). Kidney tissue that becomes necrotic during this process releases a variety of pro\u2010inflammatory factors, driving activation of the complement cascade. Complement 5 (C5), in particular, has become an important therapeutic target, yet pharmacologic targeting does not achieve complete inhibition nor target all variants of this abundant protein. Here, we have generated and characterized a novel rat model of CRISPR\/Cas9\u2010mediated global C5 deletion (C5\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ). C5\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    rats displayed no differences in growth, blood chemistry, or kidney morphology\/function from wild\u2010type (C5\n                    <jats:sup>+\/+<\/jats:sup>\n                    ) counterparts at baseline. Subsequently, we compared C5\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    rats to C5\n                    <jats:sup>+\/+<\/jats:sup>\n                    littermates in a renal IRI model to assess differences in the post\u2010injury response. Compared to C5\n                    <jats:sup>+\/+<\/jats:sup>\n                    , C5\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    rats displayed significantly improved kidney injury\/function as well as the attenuation of the apoptotic pathway post\u2010IRI. The circulating immune cell composition was affected by C5\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    post\u2010injury, with significantly increased NK cells, B cells, and CD8+ T\u2010cells compared to C5\n                    <jats:sup>+\/+<\/jats:sup>\n                    , indicating altered inflammatory signaling. Similarly, renal sections showed a reduced level of immune cell infiltration, including macrophages and neutrophils. Collectively, these results demonstrate the generation of an effective rodent model of global C5 deletion and the role of C5 as an injury\u2010promoting molecule during kidney IRI.\n                  <\/jats:p>","DOI":"10.14814\/phy2.70576","type":"journal-article","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T08:08:17Z","timestamp":1762330097000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Post\u2010ischemia and reperfusion kidney injury is mitigated in a novel complement 5 knockout rat"],"prefix":"10.14814","volume":"13","author":[{"given":"Madison","family":"McGraw","sequence":"first","affiliation":[{"name":"Department of Pharmacology &amp; Toxicology University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amod","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Toxicology University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinesh","family":"Bhattarai","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Toxicology University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neelam","family":"Joshi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Toxicology University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neriman","family":"Gokden","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong\u2010Ok","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Toxicology University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gopinath","family":"Venugopal","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Toxicology University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3994-5338","authenticated-orcid":false,"given":"Nirmala","family":"Parajuli","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Toxicology University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,5]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2017.05.012"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad1210"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40620\u2010021\u201001045\u20107"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2011.38"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523\u20101755.2003.00737.x"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010020\u201000940\u20109"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0142520"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.0000000000000384"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.72.6.1989"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2006121343"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2020.09.033"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.12405"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582\u2010020\u20100400\u20100"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2014.304"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01093"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022017860"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.05\u20104747com"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20101\u20104939\u20109581\u20103_4"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11248\u2010006\u20109002\u2010x"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0002560"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01540901"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1100338"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.110081"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10793"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/1340156"},{"key":"e_1_2_11_27_1","volume-title":"Harkness and Wagner's biology and medicine of rabbits and rodents","author":"Harkness J. 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