title: Postnatal developmental delay and supersensitivity to organophosphate in gene-targeted mice lacking acetylcholinesterase.
abstract: Acetylcholinesterase (AChE; EC 3.1.1.7) is the primary terminator of nerve impulse transmission at cholinergic synapses and is believed to play an important role in neural development. Targeted deletion of four exons of the ACHE gene reduced AChE activity by half in heterozygous mutant mice and totally eliminated AChE activity in nullizygous animals. Butyrylcholinesterase (EC 3.1.1.8) activity was normal in AChE -/- mice. Although nullizygous mice were born alive and lived up to 21 days, physical development was delayed. The neuromuscular junction of 12-day-old nullizygous animals appeared normal in structure. Nullizygous mice were highly sensitive to the toxic effects of the organophosphate diisopropylfluorophosphate and to the butyrylcholinesterase-specific inhibitor bambuterol. These findings indicate that butyrylcholinesterase and possibly other enzymes are capable of compensating for some functions of AChE and that the inhibition of targets other than AChE by organophosphorus agents results in death.
authors.affiliation: Eppley Institute, University of Nebraska Medical Center, Omaha 68198-6805, USA.
authors.forename: W
authors.initials: W
authors.lastname: Xie
authors.forename: J A
authors.initials: JA
authors.lastname: Stribley
authors.forename: A
authors.initials: A
authors.lastname: Chatonnet
authors.forename: P J
authors.initials: PJ
authors.lastname: Wilder
authors.forename: A
authors.initials: A
authors.lastname: Rizzino
authors.forename: R D
authors.initials: RD
authors.lastname: McComb
authors.forename: P
authors.initials: P
authors.lastname: Taylor
authors.forename: S H
authors.initials: SH
authors.lastname: Hinrichs
authors.forename: O
authors.initials: O
authors.lastname: Lockridge
mesh_terms: D000110:Acetylcholinesterase / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002091:Butyrylcholinesterase / Q000378:metabolism; D006128:Growth; D007531:Isoflurophate / Q000633:toxicity*; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009469:Neuromuscular Junction / Q000648:ultrastructure
chemical_list: D007531:Isoflurophate; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase