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To date, few animal models that reproduce the histological and clinical correlates of HIC have yet been established. In the present study, we aimed to develop a novel animal model for HIC via autoimmunity to the bladder urothelium using the transgenic mouse model (URO-OVA) that expresses the membrane form of the model antigen ovalbumin (OVA) as a self-antigen on the bladder urothelium. OVA-specific lymphocytes (splenocytes) were generated by immunization of C57BL\/6 mice with OVA protein and injected intravenously into URO-OVA mice. The splenocytes from OVA-immunized C57BL\/6 mice showed increased interferon (IFN)-\u03b3 production in response to OVA stimulation in vitro. URO-OVA mice adoptively transferred with OVA-primed splenocytes developed cystitis exhibiting histological chronic inflammatory changes such as remarkable mononuclear cell infiltration predominantly composed of T and B lymphocytes, increased vascularity, and mucosal hyperemia in the bladder at days 7\u2013 28 with a peak at day 21 tested. No systemic inflammation was found in cystitis-induced URO-OVA mice, nor was any inflammation found in wild-type C57BL\/6 mice adoptively transferred with OVA-primed splenocytes. Along with bladder inflammation, URO-OVA mice demonstrated significantly increased pelvic nociceptive responses, voiding dysfunction, and upregulated mRNA expression levels for IFN-\u03b3, tumor necrosis factor-\u03b1 (TNF-\u03b1), and substance P precursor in the bladder. This model reproduces the histological and clinical features of human HIC, providing a novel model for HIC research.<\/jats:p>","DOI":"10.1152\/ajprenal.00290.2020","type":"journal-article","created":{"date-parts":[[2020,12,14]],"date-time":"2020-12-14T07:17:58Z","timestamp":1607930278000},"page":"F174-F182","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":26,"title":["Autoimmunity to urothelial antigen causes bladder inflammation, pelvic pain, and voiding dysfunction: a novel animal model for Hunner-type interstitial cystitis"],"prefix":"10.1152","volume":"320","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1439-5640","authenticated-orcid":false,"given":"Yoshiyuki","family":"Akiyama","sequence":"first","affiliation":[{"name":"Department of Urology, University of Iowa, Iowa City, 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