{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T01:20:49Z","timestamp":1784164849817,"version":"3.55.0"},"reference-count":48,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,3,13]],"date-time":"2019-03-13T00:00:00Z","timestamp":1552435200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003243","name":"Ministerstvo Zdravotnictv\u00ed Cesk\u00e9 Republiky","doi-asserted-by":"publisher","award":["RVO\u2010VFN 64165"],"award-info":[{"award-number":["RVO\u2010VFN 64165"]}],"id":[{"id":"10.13039\/501100003243","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:p>The most common ureagenesis defect is X\u2010linked ornithine transcarbamylase (OTC) deficiency which is a main target for novel therapeutic interventions. The <jats:italic>spf<\/jats:italic><jats:sup>\n<jats:italic>ash<\/jats:italic><\/jats:sup> mouse model carries a variant (c.386G&gt;A, p.Arg129His) that is also found in patients. Male <jats:italic>spf<\/jats:italic><jats:sup>\n<jats:italic>ash<\/jats:italic><\/jats:sup> mice have a mild biochemical phenotype with low OTC activity (5%\u201010% of wild\u2010type), resulting in elevated urinary orotic acid but no hyperammonemia. We recently established a dried blood spot method for in vivo quantification of ureagenesis by Gas chromatography\u2013mass spectrometry (GC\u2010MS) using stable isotopes. Here, we applied this assay to wild\u2010type and <jats:italic>spf<\/jats:italic><jats:sup>\n<jats:italic>ash<\/jats:italic><\/jats:sup> mice to assess ureagenesis at different ages. Unexpectedly, we found an age\u2010dependency with a higher capacity for ammonia detoxification in young mice after weaning. A parallel pattern was observed for carbamoylphosphate synthetase 1 and OTC enzyme expression and activities, which may act as pacemaker of this ammonia detoxification pathway. Moreover, high ureagenesis in younger mice was accompanied by elevated periportal expression of hepatic glutamine synthetase, another main enzyme required for ammonia detoxification. These observations led us to perform a more extensive analysis of the <jats:italic>spf<\/jats:italic><jats:sup>\n<jats:italic>ash<\/jats:italic><\/jats:sup> mouse in comparison to the wild\u2010type, including characterization of the corresponding metabolites, enzyme activities in the liver and plasma and the gut microbiota. In conclusion, the comprehensive enzymatic and metabolic analysis of ureagenesis performed in the presented depth was only possible in animals. Our findings suggest such analyses being essential when using the mouse as a model and revealed age\u2010dependent activity of ammonia detoxification.<\/jats:p>","DOI":"10.1002\/jimd.12068","type":"journal-article","created":{"date-parts":[[2019,2,4]],"date-time":"2019-02-04T02:59:27Z","timestamp":1549249167000},"page":"1064-1076","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Comprehensive characterization of ureagenesis in the <i>spf<\/i><sup><i>ash<\/i><\/sup> mouse, a model of human ornithine transcarbamylase deficiency, reveals age\u2010dependency of ammonia detoxification"],"prefix":"10.1002","volume":"42","author":[{"given":"Gabriella","family":"Allegri","sequence":"first","affiliation":[{"name":"Division of Metabolism and Children's Research Center (CRC) University Children's Hospital Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sereina","family":"Deplazes","sequence":"additional","affiliation":[{"name":"Division of Metabolism and Children's Research Center (CRC) University Children's Hospital Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Rimann","sequence":"additional","affiliation":[{"name":"Division of Metabolism and Children's Research Center (CRC) University Children's Hospital Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Causton","sequence":"additional","affiliation":[{"name":"Kaleido Biosciences Inc.  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Hospital in Prague  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktor","family":"Ko\u017eich","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine Charles University\u2010First Faculty of Medicine and General University Hospital in Prague  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Marc","family":"Nuoffer","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry Inselspital Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiu M.","family":"Grisch\u2010Chan","sequence":"additional","affiliation":[{"name":"Division of Metabolism and Children's Research Center (CRC) University Children's Hospital Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beat","family":"Th\u00f6ny","sequence":"additional","affiliation":[{"name":"Division of Metabolism and 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