{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T17:53:57Z","timestamp":1788976437506,"version":"build-2803163510"},"reference-count":38,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,12,30]],"date-time":"2020-12-30T00:00:00Z","timestamp":1609286400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Ornithine transcarbamylase deficiency (OTCD) is a metabolic and genetic disease caused by dysfunction of the hepatocytic urea cycle. To develop new drugs or therapies for OTCD, it is ideal to use models that are more closely related to human metabolism and pathology. Primary human hepatocytes (HHs) isolated from two patients (a 6\u2010month\u2010old boy and a 5\u2010year\u2010old girl) and a healthy donor were transplanted into host mice (hemi\u2010, hetero\u2010OTCD mice, and control mice, respectively). HHs were isolated from these mice and used for serial transplantation into the next host mouse or for in vitro experiments. Histological, biochemical, and enzyme activity analyses were performed. Cultured HHs were treated with ammonium chloride or therapeutic drugs. Replacement rates exceeded 80% after serial transplantation in both OTCD mice. These highly humanized OTCD mice showed characteristics similar to OTCD patients that included increased blood ammonia levels and urine orotic acid levels enhanced by allopurinol. Hemi\u2010OTCD mice showed defects in OTC expression and significantly low enzymatic activities, while hetero\u2010OTCD mice showed residual OTC expression and activities. A reduction in ammonium metabolism was observed in cultured HHs from OTCD mice, and treatment with the therapeutic drug reduced the ammonia levels in the culture medium. In conclusion, we established in vivo OTC mouse models with hemi\u2010 and hetero\u2010patient HHs. HHs isolated from the mice were useful as an in vitro model of OTCD. These OTC models could be a source of valuable patient\u2010derived hepatocytes that would enable large scale and reproducible experiments using the same donor.<\/jats:p>","DOI":"10.1002\/jimd.12347","type":"journal-article","created":{"date-parts":[[2020,12,18]],"date-time":"2020-12-18T17:01:11Z","timestamp":1608310871000},"page":"618-628","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Humanized liver mouse model with transplanted human hepatocytes from patients with ornithine transcarbamylase deficiency"],"prefix":"10.1002","volume":"44","author":[{"given":"Go","family":"Sugahara","sequence":"first","affiliation":[{"name":"Research and Development Department PhoenixBio Co., Ltd  Higashi\u2010Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chihiro","family":"Yamasaki","sequence":"additional","affiliation":[{"name":"Research and Development Department PhoenixBio Co., Ltd  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