Abstract
The contribution of mouse models for basic and translational research at different levels is important to understand neurodegenerative diseases, including tauopathies, by studying the alterations in the corresponding mouse models in detail. Moreover, several studies demonstrated that pathological as well as behavioral changes are influenced by the sex. For this purpose, we performed an in-depth characterization of the behavioral alterations in the transgenic Tau-P301L mouse model. Sex-matched wild type and homozygous Tau-P301L mice were tested in a battery of behavioral tests at different ages. Tau-P301L male mice showed olfactory and motor deficits as well as increased Tau pathology, which was not observed in Tau-P301L female mice. Both Tau-P301L male and female mice had phenotypic alterations in the SHIRPA test battery and cognitive deficits in the novel object recognition test. This study demonstrated that Tau-P301L mice have phenotypic alterations, which are in line with the histological changes and with a sex-dependent performance in those tests. Summarized, the Tau-P301L mouse model shows phenotypic alterations due to the presence of neurofibrillary tangles in the brain.
Highlights
Tau-P301L mice (Tau) protein is a microtubule associated protein, located in the axons, which plays a major role in the stabilization of microtubules [1] and trafficking [2,3,4]
By comparison of the body weight, Tau-P301L mice had similar weight compared to wild type (WT) mice, Tau-P301L female mice had a slightly higher weight compared to WT female mice at 4 months of age (Figure S1)
Tau-P301L mice did not display any deficits in the nesting behavior and marble burying compared to WT
Summary
Tau protein is a microtubule associated protein, located in the axons, which plays a major role in the stabilization of microtubules [1] and trafficking [2,3,4]. It is expressed by the microtubule-associated protein Tau (MAPT) gene located on the chromosome 17. The isoform expression varies from 0N3R, which is the shortest form, to 2N4R, which is the longest form. The Tau binding site to the microtubules is hyperphosphorylated and results in loss of its function. Pathological Tau is present in different neurodegenerative diseases called tauopathies
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