Behaviour profile characterization of PS19 and rTg4510 tauopathy mouse models: A systematic review and a meta-analysis.

Abstract

The rTg4510 and PS19 mouse models are widely used in tauopathy research. Alzheimer's disease (AD) is the most prevalent among tauopathies. Behavioural tests are frequently used to assess emotional, cognitive, and motor behaviours in mouse models of AD. Cognitive deficits begin to manifest in rTg4510 mice around 3 months of age and in PS19 mice around 6 months. However, it's widely recognized that behavioural outcomes can vary due to environmental factors, health status, and husbandry practices, causing phenotypic differences between facilities. This study aims to consolidate current knowledge of the behavioural phenotypes of these two mouse models. We conducted a comprehensive literature review using keyword searches with Boolean operators across databases up to January 2024. Additional studies were included from manual searches. A total of 23 articles were reviewed for rTg4510 mice and 52 for PS19 mice. We extracted methodological details and key findings from each study. Results for rTg4510 mice show consistent findings regarding locomotion, memory and learning, and neurological dysfunction. However, the limited studies on motor and balance behaviour revealed no significant differences, while anxiety-like behaviour showed some inconsistencies. PS19 mice demonstrate more robust results for anxiety-like behaviour, memory and learning, and locomotion, while findings for balance and coordination are more inconsistent. Although there is overall coherence in certain aspects of the behavioural profiles of these tauopathy mouse models, it is crucial to recognize experimental heterogeneity and profile behavioural baselines to optimize the testing of both genetic and pharmacological interventions.