Evaluating the feasibility of gene replacement strategies to treat MTRFR deficiency.

ABSTRACT: Mitochondrial translation release factor in rescue (MTRFR) catalyzes a termination step in protein synthesis, facilitating release of the nascent chain from mitoribosomes. Pathogenic variants in MTRFR cause MTRFR deficiency and are loss-of-function variants. Here, we tested gene replacement as a possible therapeutic strategy. A truncating mutation (K155*) was generated in mice; however, homozygotes die embryonically whereas mice heterozygous for this K155* allele are normal. We also generated transgenic strains expressing either wild-type human MTRFR or a partially functional MTRFR. Despite dose-dependent phenotypes from overexpression in vitro, neither transgene caused adverse effects in vivo. In K155* homozygous mice, the wild-type MTRFR transgene completely rescued the phenotype with on

SUBMITTER: Pratt SL 

PROVIDER: S-EPMC12171093 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature