Missense mutation in selenocysteine synthase causes cardio-respiratory failure and perinatal death in mice which can be compensated by selenium-independent GPX4.

ABSTRACT: Selenoproteins are a small family of proteins containing the trace element selenium in form of the rare amino acid selenocysteine (Sec), which is decoded by the UGA codon. In humans, a number of pathogenic variants in genes encoding distinct selenoproteins or selenoprotein biosynthesis factors have been identified. Pathogenic variants in selenocysteine synthase (SEPSECS), which catalyzes the last step in Sec-tRNA^[Ser]Sec biosynthesis, were reported in children suffering from progressive cerebello-cerebral atrophy. To understand the pathomechanism associated with SEPSECS deficiency, we generated a novel mouse model recapitulating the respective human pathogenic p.Y334C variant in the murine Sepsecs gene (Sepsecs^Y334C). Unlike in patients, pups homozygous for the p.Y334

SUBMITTER: Fradejas-Villar N 

PROVIDER: S-EPMC8605217 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature