Winrow Christopher J, Hemming Matthew L, Allen Duane M, Quistad Gary B, Casida John E, Barlow Carrolee
The Salk Institute for Biological Studies, The Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
Nat Genet. 2003 Apr;33(4):477-85. doi: 10.1038/ng1131. Epub 2003 Mar 17.
Neuropathy target esterase (NTE) is involved in neural development and is the target for neurodegeneration induced by selected organophosphorus pesticides and chemical warfare agents. We generated mice with disruptions in Nte, the gene encoding NTE. Nte(-/-) mice die after embryonic day 8, and Nte(+/-) mice have lower activity of Nte in the brain and higher mortality when exposed to the Nte-inhibiting compound ethyl octylphosphonofluoridate (EOPF) than do wild-type mice. Nte(+/-) and wild-type mice treated with 1 mg per kg of body weight of EOPF have elevated motor activity, showing that even minor reduction of Nte activity leads to hyperactivity. These studies show that genetic or chemical reduction of Nte activity results in a neurological phenotype of hyperactivity in mammals and indicate that EOPF toxicity occurs directly through inhibition of Nte without the requirement for Nte gain of function or aging.
神经病靶酯酶（NTE）参与神经发育，是某些有机磷农药和化学战剂诱导神经退行性变的靶点。我们构建了编码NTE的基因Nte发生破坏的小鼠。Nte（-/-）小鼠在胚胎第8天后死亡，与野生型小鼠相比，Nte（+/-）小鼠脑中Nte活性较低，且在暴露于抑制Nte的化合物乙基辛基磷酰氟（EOPF）时死亡率更高。用每千克体重1毫克的EOPF处理的Nte（+/-）和野生型小鼠运动活性升高，表明即使Nte活性轻微降低也会导致多动。这些研究表明，Nte活性的遗传或化学降低会导致哺乳动物出现多动的神经学表型，并表明EOPF毒性直接通过抑制Nte发生，而无需Nte功能获得或老化。
