Animal models of Huntington's disease. Pros and cons

Modelling of human neurological diseases uses a plethora of ever-more sophisticated methods and approaches. For Huntington's disease (HD), which affects specific neuronal types and circuits in the brain, this has meant the use of both neurotoxic compounds and various animal models of different complexity, ranging from rodents to non-primate ones. Genetic models are classified based on the use of specific constructs including gene including gene fragments, full-length, knock-out and knock-in models. In this review, we will discuss the available animal models for HD, highlighting their pros and cons in studying the neuropathology, behavioural alterations, and biological mechanisms that prevail in HD and during the disease progression. We also highlight present knowledge gaps and difficulties to fully recapitulate the human disease. At the end we will further elaborate on current outstanding questions in HD research that warrant further studies using both animal models and patient data. This may help to guide future research and increase the translational relevance of the models to solve key questions and pave the way for better treatment options and design of drugs to alleviate the course of HD.