{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:18:47Z","timestamp":1760145527956,"version":"build-2065373602"},"reference-count":68,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T00:00:00Z","timestamp":1721952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["16H05134","19K07953"],"award-info":[{"award-number":["16H05134","19K07953"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Conventional rodent neuromyelitis optica spectrum disorder (NMOSD) models using patient-derived immunoglobulin G (IgG) are potentially affected by the differences between the human and rodent aquaporin-4 (AQP4) extracellular domains (ECDs). We hypothesized that the humanization of AQP4 ECDs would make the rodent model lesions closer to human NMOSD pathology. Humanized-AQP4-expressing (hAQP4) rats were generated using genome-editing technology, and the human AQP4-specific monoclonal antibody (mAb) or six patient-derived IgGs were introduced intraperitoneally into hAQP4 rats and wild-type Lewis (WT) rats after immunization with myelin basic protein and complete Freund\u2019s adjuvant. Human AQP4-specific mAb induced astrocyte loss lesions specifically in hAQP4 rats. The patient-derived IgGs also induced NMOSD-like tissue-destructive lesions with AQP4 loss, demyelination, axonal swelling, complement deposition, and marked neutrophil and macrophage\/microglia infiltration in hAQP4 rats; however, the difference in AQP4 loss lesion size and infiltrating cells was not significant between hAQP4 and WT rats. The patient-derived IgGs bound to both human and rat AQP4 M23, suggesting their binding to the shared region of human and rat AQP4 ECDs. Anti-AQP4 titers positively correlated with AQP4 loss lesion size and neutrophil and macrophage\/microglia infiltration. Considering that patient-derived IgGs vary in binding sites and affinities and some of them may not bind to rodent AQP4, our hAQP4 rat is expected to reproduce NMOSD-like pathology more accurately than WT rats.<\/jats:p>","DOI":"10.3390\/ijms25158169","type":"journal-article","created":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T14:39:08Z","timestamp":1722004748000},"page":"8169","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Humanized-Aquaporin-4-Expressing Rat Created by Gene-Editing Technology and Its Use to Clarify the Pathology of Neuromyelitis Optica Spectrum Disorder"],"prefix":"10.3390","volume":"25","author":[{"given":"Chihiro","family":"Namatame","sequence":"first","affiliation":[{"name":"Department of Neurology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6163-8794","authenticated-orcid":false,"given":"Yoichiro","family":"Abe","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Keio University School of Medicine, Tokyo 160-8582, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4020-9290","authenticated-orcid":false,"given":"Yoshiki","family":"Miyasaka","sequence":"additional","affiliation":[{"name":"Laboratory of Reproductive Engineering, Institute of Experimental Animal Sciences, Osaka University Medical School, Suita 565-0871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1071-2186","authenticated-orcid":false,"given":"Yoshiki","family":"Takai","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0163-8105","authenticated-orcid":false,"given":"Yuki","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiyuki","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan"},{"name":"Department of Neurology, National Hospital Organization Yonezawa Hospital, Yonezawa 992-1202, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoji","family":"Mashimo","sequence":"additional","affiliation":[{"name":"Division of Animal Genetics, Laboratory Animal Research Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsuro","family":"Misu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuo","family":"Fujihara","sequence":"additional","affiliation":[{"name":"Department of Multiple Sclerosis & Therapeutics, Fukushima Medical University, Fukushima 960-1295, Japan"},{"name":"Multiple Sclerosis & Neuromyelitis Optica Center, Southern Tohoku Research Institute for Neuroscience, Koriyama 963-8563, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masato","family":"Yasui","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Keio University School of Medicine, Tokyo 160-8582, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7284-1069","authenticated-orcid":false,"given":"Masashi","family":"Aoki","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1056\/NEJMra1904655","article-title":"Neuromyelitis Optica Spectrum Disorder","volume":"387","author":"Wingerchuk","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1212\/WNL.0b013e3182a6cb5c","article-title":"Updated estimate of AQP4-IgG serostatus and disability outcome in neuromyelitis optica","volume":"81","author":"Jiao","year":"2013","journal-title":"Neurology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1002\/ana.24554","article-title":"Neuromyelitis optica: Evaluation of 871 attacks and 1,153 treatment courses","volume":"79","author":"Kleiter","year":"2016","journal-title":"Ann. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Chihara, N., and Yamamura, T. (2022). Immuno-Pathogenesis of Neuromyelitis Optica and Emerging Therapies. Seminars in Immunopathology, Springer.","DOI":"10.1007\/s00281-022-00941-9"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3879","DOI":"10.1007\/s00415-024-12426-w","article-title":"Moving towards a new era for the treatment of neuromyelitis optica spectrum disorders","volume":"271","author":"Preziosa","year":"2024","journal-title":"J. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1084\/jem.20050304","article-title":"IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel","volume":"202","author":"Lennon","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1002\/ana.21837","article-title":"Neuromyelitis optica: Pathogenicity of patient immunoglobulin in vivo","volume":"66","author":"Bradl","year":"2009","journal-title":"Ann. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.bbrc.2009.06.085","article-title":"Neuromyelitis optica: Passive transfer to rats by human immunoglobulin","volume":"386","author":"Kinoshita","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1002\/ana.21802","article-title":"Intrathecal pathogenic anti-aquaporin-4 antibodies in early neuromyelitis optica","volume":"66","author":"Bennett","year":"2009","journal-title":"Ann. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/bpa.12793","article-title":"Experimental animal models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders: Progress and shortcomings","volume":"30","author":"Duan","year":"2020","journal-title":"Brain Pathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1007\/s00401-013-1204-8","article-title":"Unique neuromyelitis optica pathology produced in naive rats by intracerebral administration of NMO-IgG","volume":"127","author":"Asavapanumas","year":"2014","journal-title":"Acta Neuropathol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/2051-5960-2-48","article-title":"Neuromyelitis optica pathology in rats following intraperitoneal injection of NMO-IgG and intracerebral needle injury","volume":"2","author":"Asavapanumas","year":"2014","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1093\/jnen\/nly107","article-title":"Noninvasive, Targeted Creation of Neuromyelitis Optica Pathology in AQP4-IgG Seropositive Rats by Pulsed Focused Ultrasound","volume":"78","author":"Yao","year":"2019","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.expneurol.2014.12.015","article-title":"The intrinsic pathogenic role of autoantibodies to aquaporin 4 mediating spinal cord disease in a rat passive-transfer model","volume":"265","author":"Geis","year":"2015","journal-title":"Exp. Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5497","DOI":"10.1016\/S0021-9258(17)37486-0","article-title":"Molecular cloning of a mercurial-insensitive water channel expressed in selected water-transporting tissues","volume":"269","author":"Hasegawa","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"13052","DOI":"10.1073\/pnas.91.26.13052","article-title":"Molecular characterization of an aquaporin cDNA from brain: Candidate osmoreceptor and regulator of water balance","volume":"91","author":"Jung","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4328","DOI":"10.1073\/pnas.92.10.4328","article-title":"Immunolocalization of the mercurial-insensitive water channel and glycerol intrinsic protein in epithelial cell plasma membranes","volume":"92","author":"Frigeri","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2506","DOI":"10.1523\/JNEUROSCI.18-07-02506.1998","article-title":"Aquaporin-4 water channel protein in the rat retina and optic nerve: Polarized expression in M\u00fcller cells and fibrous astrocytes","volume":"18","author":"Nagelhus","year":"1998","journal-title":"J. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1523\/JNEUROSCI.17-01-00171.1997","article-title":"Specialized membrane domains for water transport in glial cells: High-resolution immunogold cytochemistry of aquaporin-4 in rat brain","volume":"17","author":"Nielsen","year":"1997","journal-title":"J. Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"22907","DOI":"10.1074\/jbc.270.39.22907","article-title":"cDNA cloning, gene organization, and chromosomal localization of a human mercurial insensitive water channel. Evidence for distinct transcriptional units","volume":"270","author":"Yang","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"10908","DOI":"10.1073\/pnas.93.20.10908","article-title":"The human AQP4 gene: Definition of the locus encoding two water channel polypeptides in brain","volume":"93","author":"Lu","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1006\/geno.1997.4641","article-title":"Cloning and chromosomal localization of mouse aquaporin 4: Exclusion of a candidate mutant phenotype, ataxia","volume":"41","author":"Turtzo","year":"1997","journal-title":"Genomics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4577","DOI":"10.1074\/jbc.271.9.4577","article-title":"The mercurial insensitive water channel (AQP-4) forms orthogonal arrays in stably transfected Chinese hamster ovary cells","volume":"271","author":"Yang","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2855","DOI":"10.1242\/jcs.110.22.2855","article-title":"Absence of orthogonal arrays in kidney, brain and muscle from transgenic knockout mice lacking water channel aquaporin-4","volume":"110","author":"Verbavatz","year":"1997","journal-title":"J. Cell Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"11981","DOI":"10.1073\/pnas.95.20.11981","article-title":"Direct immunogold labeling of aquaporin-4 in square arrays of astrocyte and ependymocyte plasma membranes in rat brain and spinal cord","volume":"95","author":"Rash","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"13609","DOI":"10.1073\/pnas.2235843100","article-title":"Aquaporin-4 square array assembly: Opposing actions of M1 and M23 isoforms","volume":"100","author":"Furman","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"F501","DOI":"10.1152\/ajprenal.00439.2003","article-title":"Membrane organization and function of M1 and M23 isoforms of aquaporin-4 in epithelial cells","volume":"287","author":"Silberstein","year":"2004","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1620\/tjem.210.307","article-title":"Establishment of a new sensitive assay for anti-human aquaporin-4 antibody in neuromyelitis optica","volume":"210","author":"Takahashi","year":"2006","journal-title":"Tohoku J. Exp. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.1212\/01.WNL.0000289761.64862.ce","article-title":"Pathogenic potential of IgG binding to water channel extracellular domain in neuromyelitis optica","volume":"69","author":"Hinson","year":"2007","journal-title":"Neurology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e1034","DOI":"10.1212\/NXI.0000000000001034","article-title":"Molecular Level Characterization of Circulating Aquaporin-4 Antibodies in Neuromyelitis Optica Spectrum Disorder","volume":"8","author":"Li","year":"2021","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.jneuroim.2009.04.001","article-title":"Identification of binding sites for anti-aquaporin 4 antibodies in patients with neuromyelitis optica","volume":"211","author":"Tani","year":"2009","journal-title":"J. Neuroimmunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"12123","DOI":"10.1074\/jbc.M115.647149","article-title":"Mutagenesis of the aquaporin 4 extracellular domains defines restricted binding patterns of pathogenic neuromyelitis optica IgG","volume":"290","author":"Owens","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1186\/s12974-016-0642-3","article-title":"Characterization of the binding pattern of human aquaporin-4 autoantibodies in patients with neuromyelitis optica spectrum disorders","volume":"13","author":"Tuller","year":"2016","journal-title":"J. Neuroinflamm."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.jneuroim.2013.03.003","article-title":"Establishment of monoclonal antibodies against the extracellular domain that block binding of NMO-IgG to AQP4","volume":"260","author":"Miyazaki","year":"2013","journal-title":"J. Neuroimmunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/s40478-015-0259-2","article-title":"Severely exacerbated neuromyelitis optica rat model with extensive astrocytopathy by high affinity anti-aquaporin-4 monoclonal antibody","volume":"3","author":"Kurosawa","year":"2015","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1007\/s00401-013-1116-7","article-title":"Presence of six different lesion types suggests diverse mechanisms of tissue injury in neuromyelitis optica","volume":"125","author":"Misu","year":"2013","journal-title":"Acta Neuropathol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2401","DOI":"10.1093\/brain\/awab102","article-title":"Staging of astrocytopathy and complement activation in neuromyelitis optica spectrum disorders","volume":"144","author":"Takai","year":"2021","journal-title":"Brain"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1093\/brain\/awf151","article-title":"A role for humoral mechanisms in the pathogenesis of Devic\u2019s neuromyelitis optica","volume":"125","author":"Lucchinetti","year":"2002","journal-title":"Brain"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/s41591-022-02176-5","article-title":"Base editing correction of hypertrophic cardiomyopathy in human cardiomyocytes and humanized mice","volume":"29","author":"Chai","year":"2023","journal-title":"Nat. Med."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Lebek, S., Caravia, X.M., Straub, L.G., Alzhanov, D., Tan, W., Li, H., McAnally, J.R., Chen, K., Xu, L., and Scherer, P.E. (2024). CRISPR-Cas9 base editing of pathogenic CaMKII\u03b4 improves cardiac function in a humanized mouse model. J. Clin. Investig., 134.","DOI":"10.1172\/JCI175164"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.molimm.2014.06.003","article-title":"Inhibitor(s) of the classical complement pathway in mouse serum limit the utility of mice as experimental models of neuromyelitis optica","volume":"62","author":"Ratelade","year":"2014","journal-title":"Mol. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Rodin, R.E., and Chitnis, T. (2024). Soluble biomarkers for Neuromyelitis Optica Spectrum Disorders: A mini review. Front. Neurol., 15.","DOI":"10.3389\/fneur.2024.1415535"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1093\/brain\/awm062","article-title":"Anti-aquaporin-4 antibody is involved in the pathogenesis of NMO: A study on antibody titre","volume":"130","author":"Takahashi","year":"2007","journal-title":"Brain"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Liu, J., Tan, G., Li, B., Zhang, J., Gao, Y., Cao, Y., Jia, Z., and Sugimoto, K. (2021). Serum Aquaporin 4-Immunoglobulin G Titer and Neuromyelitis Optica Spectrum Disorder Activity and Severity: A Systematic Review and Meta-Analysis. Front. Neurol., 12.","DOI":"10.3389\/fneur.2021.746959"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"120293","DOI":"10.1016\/j.jns.2022.120293","article-title":"Possible role of neutrophils in astrocyte injury in neuromyelitis optica spectrum disorder","volume":"438","author":"Kobayashi","year":"2022","journal-title":"J. Neurol. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/s40478-019-0766-7","article-title":"Complement-independent bystander injury in AQP4-IgG seropositive neuromyelitis optica produced by antibody-dependent cellular cytotoxicity","volume":"7","author":"Duan","year":"2019","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1002\/ana.22686","article-title":"Neutrophil protease inhibition reduces neuromyelitis optica-immunoglobulin G-induced damage in mouse brain","volume":"71","author":"Saadoun","year":"2012","journal-title":"Ann. Neurol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e1149","DOI":"10.1212\/NXI.0000000000001149","article-title":"Cell-Free DNA Derived From Neutrophils Triggers Type 1 Interferon Signature in Neuromyelitis Optica Spectrum Disorder","volume":"9","author":"Murata","year":"2022","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.jneuroim.2011.03.007","article-title":"T cell deficiency does not reduce lesions in mice produced by intracerebral injection of NMO-IgG and complement","volume":"235","author":"Saadoun","year":"2011","journal-title":"J. Neuroimmunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1097\/WCO.0000000000000551","article-title":"Mechanisms for lesion localization in neuromyelitis optica spectrum disorders","volume":"31","author":"Bradl","year":"2018","journal-title":"Curr. Opin. Neurol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1111\/jnc.14339","article-title":"Mechanisms underlying lesion development and lesion distribution in CNS autoimmunity","volume":"146","author":"Lindner","year":"2018","journal-title":"J. Neurochem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1007\/s00401-015-1501-5","article-title":"Highly encephalitogenic aquaporin 4-specific T cells and NMO-IgG jointly orchestrate lesion location and tissue damage in the CNS","volume":"130","author":"Zeka","year":"2015","journal-title":"Acta Neuropathol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/0165-5728(82)90037-6","article-title":"Immunocytochemical study of myelin-associated glycoprotein (MAG) and basic protein (BP) in acute experimental allergic encephalomyelitis (EAE)","volume":"3","author":"Itoyama","year":"1982","journal-title":"J. Neuroimmunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/S0730-725X(98)00216-1","article-title":"Correlation between MRI and clinico-pathological manifestations in Lewis rats protected from experimental allergic encephalomyelitis by acylated synthetic peptide of myelin basic protein","volume":"17","author":"Karlik","year":"1999","journal-title":"Magn. Reson. Imaging"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"107827","DOI":"10.1016\/j.neuropharm.2019.107827","article-title":"Affinity-matured \u2018aquaporumab\u2019 anti-aquaporin-4 antibody for therapy of seropositive neuromyelitis optica spectrum disorders","volume":"162","author":"Duan","year":"2020","journal-title":"Neuropharmacology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"13829","DOI":"10.1074\/jbc.M112.344325","article-title":"Complement-dependent cytotoxicity in neuromyelitis optica requires aquaporin-4 protein assembly in orthogonal arrays","volume":"287","author":"Phuan","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2000","DOI":"10.1172\/JCI122942","article-title":"Membrane assembly of aquaporin-4 autoantibodies regulates classical complement activation in neuromyelitis optica","volume":"129","author":"Soltys","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"21962","DOI":"10.1038\/s41598-021-01294-3","article-title":"Cytoprotective IgG antibodies in sera from a subset of patients with AQP4-IgG seropositive neuromyelitis optica spectrum disorder","volume":"11","author":"Tradtrantip","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1093\/intimm\/dxr056","article-title":"Increased T-cell immunity against aquaporin-4 and proteolipid protein in neuromyelitis optica","volume":"23","author":"Matsuya","year":"2011","journal-title":"Int. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"578109","DOI":"10.1016\/j.jneuroim.2023.578109","article-title":"Intradermal AQP4 peptide immunization induces clinical features of neuromyelitis optica spectrum disorder in mice","volume":"380","author":"Serizawa","year":"2023","journal-title":"J. Neuroimmunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1186\/s12974-022-02623-7","article-title":"A novel aquaporin-4-associated optic neuritis rat model with severe pathological and functional manifestations","volume":"19","author":"Morita","year":"2022","journal-title":"J. Neuroinflamm."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/bph.13340","article-title":"High avidity chimeric monoclonal antibodies against the extracellular domains of human aquaporin-4 competing with the neuromyelitis optica autoantibody, NMO-IgG","volume":"173","author":"Takai","year":"2016","journal-title":"Br. J. Pharmacol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"W242","DOI":"10.1093\/nar\/gky354","article-title":"CRISPOR: Intuitive guide selection for CRISPR\/Cas9 genome editing experiments and screens","volume":"46","author":"Concordet","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"10431","DOI":"10.1038\/ncomms10431","article-title":"ssODN-mediated knock-in with CRISPR-Cas for large genomic regions in zygotes","volume":"7","author":"Yoshimi","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Miyasaka, Y., Uno, Y., Yoshimi, K., Kunihiro, Y., Yoshimura, T., Tanaka, T., Ishikubo, H., Hiraoka, Y., Takemoto, N., and Tanaka, T. (2018). CLICK: One-step generation of conditional knockout mice. BMC Genom., 19.","DOI":"10.1186\/s12864-018-4713-y"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1212\/WNL.0000000000001729","article-title":"International consensus diagnostic criteria for neuromyelitis optica spectrum disorders","volume":"85","author":"Wingerchuk","year":"2015","journal-title":"Neurology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"pdb-prot099127","DOI":"10.1101\/pdb.prot099127","article-title":"Preparation of Antibody Using Caprylic Acid","volume":"2018","author":"Fishman","year":"2018","journal-title":"Cold Spring Harb. Protoc."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/15\/8169\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:24:18Z","timestamp":1760109858000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/15\/8169"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,26]]},"references-count":68,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["ijms25158169"],"URL":"https:\/\/doi.org\/10.3390\/ijms25158169","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2024,7,26]]}}}