Trappc4 is required for early mammalian development.

Abstract

Trafficking Protein Particle Complex Subunit 4 (TRAPPC4) is essential for protein transport from the endoplasmic reticulum to the Golgi apparatus. It plays a crucial role in tethering COPII vesicles and assembling SNARE complexes, ensuring precise protein delivery, which is vital for cellular communication and growth. Mutations in TRAPPC4 and other TRAPP subunits are associated with a group of human diseases collectively known as TRAPPopathies, often manifesting as neurological disorders. This study investigates the role of TRAPPC4 during early embryonic development by analysing the phenotypic consequences when the gene is knocked out in the mouse. Our results show that TRAPPC4 knockout leads to early embryonic lethality, where TRAPPC4 homozygous mutant embryos form morphologically normal blastocysts but fail to implant in the uterus and are not present at embryonic day 7.5. We show that mutant embryos can hatch from the zona pellucida, but do not form proper inner cell mass (ICM) outgrowths. Unlike the tightly compressed ICM colonies in control littermates, the mutant ICM appears necrotic with cells that are not adherent. This dispersion suggests that ICM cells may begin deteriorating at peri-implantation stages, underscoring TRAPPC4's pivotal role in maintaining cellular viability during early embryonic development.