Isoleucyl‑tRNA synthetase 1 is essential for embryogenesis in mice

Abstract

Isoleucyl-tRNA synthetase 1 (IARS1) is essential for protein synthesis. Although IARS1 mutations cause growth and metabolic disorders in humans, its role in embryonic development remains unclear. We generated Iars1 knockout (KO) mice and observed complete absence of homozygous KOs among 44 pups, indicating embryonic lethality. A χ² test confirmed significant deviation from Mendelian ratios. At E12.5, multiple resorbed implantation sites were observed, and histology at E9.5 showed embryos lacking recognizable structures. Evidence of implantation (decidual swellings with residual trophoblast and maternal vasculature) indicates post-implantation survival but failure to progress beyond early organogenesis. These results demonstrate that IARS1 is indispensable for early mouse development and provide a useful model to study the link between IARS1 deficiency and disrupted organogenesis.