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Moreover, CBS is important for the production of cysteine, hydrogen sulfide (H\n                    <jats:sub>2<\/jats:sub>\n                    S) and glutathione. Studying the biological role of CBS in adult mice has been severely hampered by embryological disturbances and perinatal mortality. To overcome these issues and assess the effects of whole\u2010body CBS deficiency in adult mice, we engineered and characterized a Cre\u2010inducible\n                    <jats:italic>Cbs<\/jats:italic>\n                    knockout model during ageing. No perinatal mortality occurred before\n                    <jats:italic>Cbs<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    induction at 10\u00a0weeks of age. Mice were followed until 90\u00a0weeks of age and ablation of\n                    <jats:italic>Cbs<\/jats:italic>\n                    was confirmed in liver and kidney but not in brain. Severe HHCy was observed in\n                    <jats:italic>Cbs<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    (289 \u00b1 58\u00a0\u00b5M) but not in\n                    <jats:italic>Cbs<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    or control mice (&lt;10\u00a0\u00b5M).\n                    <jats:italic>Cbs<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    showed impaired growth, facial alopecia, endothelial dysfunction in absence of increased mortality, and signs of liver or kidney damage. CBS expression in skin localized to sebaceous glands and epidermis, suggesting local effects of\n                    <jats:italic>Cbs<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    on alopecia.\n                    <jats:italic>Cbs<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    showed increased markers of oxidative stress and senescence but expression of other H\n                    <jats:sub>2<\/jats:sub>\n                    S producing enzymes (CSE and 3\u2010MST) was not affected. CBS deficiency severely impaired H\n                    <jats:sub>2<\/jats:sub>\n                    S production capacity in liver, but not in brain or kidney. In summary,\n                    <jats:italic>Cbs<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice presented a mild phenotype without mortality despite severe HHCy. The findings demonstrate that HHCy is not directly linked to development of end organ damage.\n                  <\/jats:p>","DOI":"10.1096\/fj.202101550r","type":"journal-article","created":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T10:46:03Z","timestamp":1647945963000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Homozygous whole body\n                    <i>Cbs<\/i>\n                    knockout in adult mice features minimal pathology during ageing despite severe homocysteinemia"],"prefix":"10.1096","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0900-0130","authenticated-orcid":false,"given":"D.","family":"Nakladal","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology University of Groningen University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. P. H.","family":"Lambooy","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology University of Groningen University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Mi\u0161\u00fath","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology University of Groningen University Medical Center Groningen  Groningen The Netherlands"},{"name":"Department of Pharmacology &amp; Toxicology Faculty of Pharmacy Comenius University in Bratislava  Bratislava Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"\u010cepcov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology University of Groningen University Medical Center Groningen  Groningen The Netherlands"},{"name":"Department of Pharmacology &amp; Toxicology Faculty of Pharmacy Comenius University in Bratislava  Bratislava Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. P.","family":"Joschko","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology University of Groningen University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"van Buiten","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology University of Groningen University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Goris","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology University of Groningen University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Hoogstra\u2010Berends","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology University of Groningen University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N. 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