Mutations in Homocysteine Metabolism Genes Increase Keratin N-Homocysteinylation and Damage in Mice

The study concluded that mutations in homocysteine metabolism genes (Cbs, Cse, and Mthfr) in mice led to increased N-homocysteinylation of keratin, resulting in significant keratin damage. This was evidenced by reduced solubility of keratin in sodium dodecyl sulfate, with mutant mice showing much lower solubility compared to wild-type mice. The findings suggested that elevated homocysteine levels could impair protein function and structure, potentially contributing to connective tissue abnormalities and other pathological conditions, thereby providing insights into hair and skin disorders associated with hyperhomocysteinemia.