Targeted disruption of the gene encoding the proteolipid subunit of mouse vacuolar H(+)-ATPase leads to early embryonic lethality.
Vacuolar 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.
Inoue
H
H
Department of Biological Science, Graduate School of Science, Osaka University, Machikaneyama-cho 1-16, Toyonaka city, Osaka, Japan.
Noumi
T
T
Nagata
M
M
Murakami
H
H
Kanazawa
H
H
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002470:Cell Survival; D003433:Crosses, Genetic; D020964:Embryo Loss / Q000235:genetics*; D005838:Genotype; D006579:Heterozygote; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D011510:Proteolipids / Q000235:genetics*; D006180:Proton-Translocating ATPases / Q000737:chemistry / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D025262:Vacuolar Proton-Translocating ATPases
D011510:Proteolipids; D012333:RNA, Messenger; D025262:Vacuolar Proton-Translocating ATPases; D006180:Proton-Translocating ATPases