Homozygous null mice have an embryonic lethal phenotype, failing to develop past embryonic day 8.5. Mice that are heterozygous for the targeted mutation are viable, fertile, normal in size and are more active than wildtype littermates. A reduced level of protein gene product is detected by immunoprecipitation and Western blot analysis of brain, testes and kidney, but protein levels are not reduced in liver. Beta galactosidase activity in heterozygotes aged embryonic day 13.5 is found in the developing lens and spinal cord. In adult heterozygotes, beta galactosidase activity is detected throughout the brain, especially in the cerebellar Purkinje cells and hippocampus. Beta galactosidase activity patterns mimic the endogenous gene expression pattern. NTE activity in brain tissue is reduced by 40%. Heterozygotes are more sensitive to organophosphate toxicity with increased motor activity and mortality. This mutant mouse strain may be useful in studies of neuropathological hyperactivity, Gulf War Syndrome, and organophosphate-induced sub-acute neurotoxicity.

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These <i> Pnpla6</i> knock-out mice exhibit an embryonic lethal phenotype, and neuropathy target esterase activity in brain tissue is reduced.

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