Spongiform pathology in mouse CNS lacking ‘neuropathy target esterase’ and cellular prion protein

Conditional inactivation of the ‘neuropathy target esterase’ (NTE) gene in mouse nerve cells was previously shown to result in CNS pathology comparable to the spongiform encephalopathy characteristic of prion diseases. To determine whether cellular prion protein (PrPc) is essential for development of this pathology we examined hippocampi of mice lacking NTE alone, PrPc alone or both NTE and PrPc. Light microscopic survey showed clear-cut spongiform changes in a majority of NTE−/− and NTE/PrP−/− double knockout mice but in only one PrP−/− mouse. EM analysis of spongiform lesions from NTE−/− and NTE/PrP−/− mice, and from the one affected PrP−/− mouse, revealed patches of branching tubular inclusions, comparable to the ‘tubulovesicular inclusions’ described previously in prion diseases. We conclude that spongiform pathology in conditional NTE knockout mice is not mediated by PrPc, and that tubulovesicular inclusions can be seen in spongiform encephalopathy of other etiologies and are not pathognomonic of prion disease.