Behavioural phenotypes rescued in Tau Knock-out mice by human Tau re-expression

ANA DAMIANICH; SONIA ESPINDOLA; ELENA AVALE

Huerta Grande, Cordoba

Congreso; XXIX Reunion Anual de la Sociedad Argentina de Investigaciones en Neurociencias; 2014

Sociedad Argentina de Investigaciones en Neurociencias

Tau is a microtubule-associated protein predominantly expressed in neurons and involved in many neuronal processes. However, the essential role of Tau in the adult brain is still controversial. Early evidence demonstrated that no gross behavioural nor neurochemical dysfunctions were observed in TauKO mice. However, recent reports suggest that the lack of Tau might be detrimental in aged mice. The aims of this work are: 1) to further evaluate the behavioral phenotypes of middle-aged TauKO mice; 2) to assess whether expression of human Tau leads to any phenotypic rescue in TauKO mice and 3) to analyze if Tau isoforms content is related to the phenotypic rescue. The ?rescued ? group are TauKO mice on which Tau expression was restored by the human Tau transgene (Htau). Wild-Type, TauKO and Htau mice were analyzed in the open field and the rotarod to assess spontaneous locomotion and motor coordination. Cognitive performance was tested in the novel object recognition (NOR) task. Tau isoforms content (depending on exon 10 alternative splicing) was determined by qPCR. Together, our results show that the lack of Tau has a significant effect over motor and cognitive behaviours, and that Tau re-expression in Htau mice fully rescues motor phenotypes but not the deficit in the NOR test. The molecular analyses so far indicate that the human tau transgene has specific splicing patterns in the mouse brain, which might underlie such differences in the behavioural rescue.