Fatal Epileptic Seizures in Mice Having Compromised Glutathione and Ascorbic Acid Biosynthesis.

ABSTRACT: Reduced glutathione (GSH) and ascorbic acid (AA) are the two most abundant low-molecular-weight antioxidants in mammalian tissues. Gclm^KO knockout mice lack the gene encoding the modifier subunit of the rate-limiting enzyme in GSH biosynthesis; Gclm^KO mice exhibit 10-40% of normal tissue GSH levels and show no overt phenotype. Gulo^KO knockout mice, lacking a functional Gulo gene encoding L-gulono-γ-lactone oxidase, cannot synthesize AA and depend on dietary ascorbic acid for survival. To elucidate functional crosstalk between GSH and AA in vivo, we generated the Gclm^KO/Gulo^KO double-knockout (DKO) mouse. DKO mice exhibited spontaneous epileptic seizures, proceeding to death between postnatal da

SUBMITTER: Chen Y 

PROVIDER: S-EPMC9952205 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature