Acidic endomembrane organelles are required for mouse postimplantation development

Vacuolar-type H+-ATPase (V-ATPase) plays a major role in endomembrane and p lasma membrane proton transport in eukaryotes. We found that the acidic com partments generated by V-ATPase are present from the one-cell stage of mous e preimplantation embryos. Upon differentiation of trophoblasts and the inn er cell mass at the blastocyst stage, these compartments exhibited a polari zed perinuclear distribution. PL16(-/-) embryos, lacking the V-ATPase 16-kD a proteolipid (c subunit), developed to the blastocyst stage and were impla nted in the uterine epithelium, but died shortly thereafter. This mutant sh owed severe defects in development of the embryonic and extraembryonic tiss ues at a stage that coincided with rapid cell proliferation. When cultured in vitro, PL16(-/-) blastocysts could hatch and become attached to the surf ace of a culture dish, but the inner cell mass grew significantly slower an d most cells failed to survive for more than 4 days. PL16(-/-) cells showed impaired endocytosis as well as organellar acidification. The Golgi comple x became swollen and vacuolated, possibly due to the absence of the luminal acidic pH, These results clearly indicate that acidic compartments are ess ential for development after implantation. (C) 2000 Academic Press.