Neuropathy Target Esterase in Brain Function and Deterioration Caused by Cholinesterase Inhibiting Chemicals.

摘要

Neuropathy target esterase (NTE) is a membrane-associated protein with serine esterase activity. A class of organophosphate (OP) compounds, used in insecticides and as chemical weapons, are capable of inhibiting NTE and lead to progressive neuropathies. We were able to isolate and characterize the human and mouse NTE (mNTE) genomic loci. We also identified a second member of the NTE family. Transgenic mice with a disrupted mNTE gene and which express the beta-galactosidase gene under the endogenous mNTE promoter were generated. Analyses demonstrated that mNTE is essential for emobryonic development and that mNTE is highly expressed in the developing spinal cord and eye, as well as in the testes and throughout the brain. Heterozygous mice have a 39% decrease in brain enzyme activity and increased mortality after exposure to NTE-inhibing EOPFs. Wid-type mice treated with low amount of EOPF and untreated mNTE heterozygous mice show elevated motor activity, suggesting that partial inhibition of NTE activity leads to hyperactivity. Further analysis of these mice also allowed us to identify NTE as a lysophospholipase.