Targeted disruption of the gene encoding the proteolipid subunit of mouse vacuolar H+-ATPase leads to early embryonic lethality

AbstractVacuolar H+-ATPase (V-ATPase) is responsible for acidification of intracellular compartments in eukaryotic cells. Its 16-kDa subunit (proteolipid, PL16) plays a central role in V-ATPase function, forming the principal channel via which protons are translocated. To elucidate physiological roles of V-ATPase in mammalian cell function and embryogenesis, we attempted to generate a PL16 null mutant mouse by gene-targeting. Mice heterozygous (PL16+/−) for the proteolipid mutation were intercrossed and their offspring were classified according to genotype. There were no homozygous (PL16−/−) pups among 69 neonates examined, but a few PL16−/− embryos were found during the pre-implantation stages of embryonic development, up to day 3.5 post-coitum. These results suggested that PL16 (and hence V-ATPase) may play an essential role in cell proliferation and viability during early embryogenesis. PL16+/− mice were indistinguishable from their wild-type littermates and displayed no discernible abnormalities, although the PL16 mRNA level in PL16+/− mice decreased to about one-half of wild-type levels