Homozygous Whole Body Cbs Knockout in Adult Mice Features Minimal Pathology During Aging Despite Severe Homocysteinemia

    March 2022 in “ ˜The œFASEB journal ”
    Dalibor Nakládal, Sebastiaan Lambooy, Svetozár Mišúth, Diana Čepcová, Christian P. Joschko, Azuwerus van Buiten, Maaike Goris, F Hoogstra-Berends, Niels J. Kloosterhuis, Nicolette Huijkman, Bart van de Sluis, Gilles F.H. Diercks, J. H. Buikema, Robert H. Henning, Leo E. Deelman
    Studysummary This study observed that mice with a whole-body deficiency of Cystathionine-β-synthase developed severe hyperhomocysteinemia and related mild symptoms without increased mortality, indicating HHCy may not directly cause end organ damage.
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    The study developed a tamoxifen-induced Cre/LoxP Cbs−/− mouse model to investigate the effects of CBS deficiency and severe homocysteinemia (HHCy). Despite severe HHCy, the mice showed minimal pathology during aging, including no significant organ damage, but did exhibit facial alopecia, endothelial dysfunction, and increased oxidative stress. The alopecia was linked to disturbed follicular integrity rather than skin thickness. The findings suggest that HHCy alone does not drive end-organ damage and highlight the role of CBS in hair maintenance, particularly in sebaceous glands.
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