{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T05:27:12Z","timestamp":1790054832568,"version":"4.0.1"},"reference-count":24,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:p>\n                    Karyomegalic interstitial nephritis (KIN) is a chronic interstitial nephropathy characterized by tubulointerstitial nephritis and formation of enlarged nuclei in the kidneys and other tissues. We recently reported that recessive mutations in the gene encoding FANCD2\/FANCI-associated nuclease 1 (FAN1) cause KIN in humans. FAN1 is a major component of the Fanconi anemia\u2013related pathway of DNA damage response (DDR) signaling. To study the pathogenesis of KIN, we generated a\n                    <jats:italic toggle=\"yes\">Fan1<\/jats:italic>\n                    knockout mouse model, with abrogation of\n                    <jats:italic toggle=\"yes\">Fan1<\/jats:italic>\n                    expression confirmed by quantitative RT-PCR. Challenging\n                    <jats:italic toggle=\"yes\">Fan1\u2212\/\u2212<\/jats:italic>\n                    and wild-type mice with 20 mg\/kg cisplatin caused AKI in both genotypes. In contrast, chronic injection of cisplatin at 2 mg\/kg induced KIN that led to renal failure within 5 weeks in\n                    <jats:italic toggle=\"yes\">Fan1\u2212\/\u2212<\/jats:italic>\n                    mice but not in wild-type mice. Cell culture studies showed decreased survival and reduced colony formation of\n                    <jats:italic toggle=\"yes\">Fan1\u2212\/\u2212<\/jats:italic>\n                    mouse embryonic fibroblasts and bone marrow mesenchymal stem cells compared with wild-type counterparts in response to treatment with genotoxic agents, suggesting that\n                    <jats:italic toggle=\"yes\">FAN1<\/jats:italic>\n                    mutations cause chemosensitivity and bone marrow failure. Our data show that Fan1 is involved in the physiologic response of kidney tubular cells to DNA damage, which contributes to the pathogenesis of CKD. Moreover,\n                    <jats:italic toggle=\"yes\">Fan1\u2212\/\u2212<\/jats:italic>\n                    mice provide a new model with which to study the pathomechanisms of CKD.\n                  <\/jats:p>","DOI":"10.1681\/asn.2015101108","type":"journal-article","created":{"date-parts":[[2016,3,29]],"date-time":"2016-03-29T21:58:33Z","timestamp":1459288713000},"page":"3552-3559","source":"Crossref","is-referenced-by-count":29,"title":["A FANCD2\/FANCI-Associated Nuclease 1-Knockout Model Develops Karyomegalic Interstitial Nephritis"],"prefix":"10.1681","volume":"27","author":[{"given":"Rannar","family":"Airik","sequence":"first","affiliation":[{"name":"Department of Medicine, Boston Children\u2019s Hospital, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Schueler","sequence":"additional","affiliation":[{"name":"Department of Medicine, Boston Children\u2019s Hospital, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merlin","family":"Airik","sequence":"additional","affiliation":[{"name":"Department of Medicine, Boston Children\u2019s Hospital, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jang","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Medicine, Boston Children\u2019s Hospital, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan D.","family":"Porath","sequence":"additional","affiliation":[{"name":"Department of Medicine, Boston Children\u2019s Hospital, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elina","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunder","family":"Sims-Lucas","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friedhelm","family":"Hildebrandt","sequence":"additional","affiliation":[{"name":"Department of Medicine, Boston Children\u2019s Hospital, Boston, Massachusetts;"},{"name":"Howard Hughes Medical Institute, Chevy Chase, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2016,3,29]]},"reference":[{"key":"B1-20231016","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1038\/ng.2347","article-title":"FAN1 mutations cause karyomegalic interstitial nephritis, linking chronic kidney failure to defective DNA damage 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