Peripheral nervous system effects in the PS19 tau transgenic mouse model of tauopathy

Abstract

It is well known that transgenic mice overexpressing human tau protein with P301S mutation driven by the mouse prion protein promoter show clasping and limb retraction, hunched back and paralysis, followed by inability to feed that results in death around 12 months of age. To understand these motor deficits, we have carried out rotarod tests on PS19 line and demonstrated how they worsened during aging. Then, we have analyzed if these phenotypic characteristics correlate with sciatic nerve degeneration. We first demonstrated by western blot and immunohistochemistry that the sciatic nerve expresses the transgenic tau protein; then, electron microscopy studies showed alterations in myelin, mainly a detachment of myelin lamellae at Schmidt-Lanterman clefts. Similar motor deficits and myelin alterations have been previously reported in tau knockout and overexpressing transgenic mice; taking into account that PS19 model is widely used to study tauopathies, we suggest that analyzing the expression of transgenic tau protein and myelin abnormalities in the sciatic nerve should be considered when studying some features as motor performance or survival. ; Spanish Ministry of Economy and Competitiveness (BFU2016-77885-P), Comunidad de Madrid cofinanced with the Structural Funds of the European Union (S2017/BMD-3700 (NEUROMETAB-CM)), Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, ISCIII), and from an institutional grant from the Fundación R. Areces