Postnatal developmental delay and supersensitivity to organophosphate in gene-targeted mice lacking acetylcholinesterase.
Postnatal developmental delay and supersensitivity to organophosphate in gene-targeted mice lacking acetylcholinesterase.
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发表时间：
2000-06
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通讯作者：
Weihua Xie;J. Stribley;Arnaud Chatonnet;Phillip J. Wilder;Angie Rizzino;Rodney D. McComb;P. Taylor;Steven H. Hinrichs;O. Lockridge
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作者：
Weihua Xie;J. Stribley;Arnaud Chatonnet;Phillip J. Wilder;Angie Rizzino;Rodney D. McComb;P. Taylor;Steven H. Hinrichs;O. Lockridge
乙酰胆碱酯酶（AChE; EC 3.1.1.7）是胆碱能突触处神经冲动传递的主要终止剂，并且被认为在神经发育中起重要作用。有针对性地删除ACHE基因的四个外显子，使杂合子突变小鼠的AChE活性降低一半，并完全消除了无效合子动物的AChE活性。丁酰胆碱酯酶（EC 3.1.1.8）活性在AChE -/-小鼠中正常。尽管非合子小鼠出生时是活的，并且存活了21天，但身体发育延迟。12日龄失合子动物的神经肌肉接头结构正常。非合子小鼠对有机磷二异丙基氟磷酸盐和丁酰胆碱酯酶特异性抑制剂班布特罗的毒性作用高度敏感。这些研究结果表明，丁酰胆碱酯酶和可能的其他酶能够补偿乙酰胆碱酯酶的某些功能，有机磷制剂对乙酰胆碱酯酶以外的靶点的抑制会导致死亡。
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.