High-Throughput Automated Phenotyping of Two Genetic Mouse Models of Huntington's Disease

PLoS Curr. 2013 Jul 11;5:ecurrents.hd.124aa0d16753f88215776fba102ceb29. doi: 10.1371/currents.hd.124aa0d16753f88215776fba102ceb29.

Abstract

Phenotyping with traditional behavioral assays constitutes a major bottleneck in the primary screening, characterization, and validation of genetic mouse models of disease, leading to downstream delays in drug discovery efforts. We present a novel and comprehensive one-stop approach to phenotyping, the PhenoCube™. This system simultaneously captures the cognitive performance, motor activity, and circadian patterns of group-housed mice by use of home-cage operant conditioning modules (IntelliCage) and custom-built computer vision software. We evaluated two different mouse models of Huntington's Disease (HD), the R6/2 and the BACHD in the PhenoCube™ system. Our results demonstrated that this system can efficiently capture and track alterations in both cognitive performance and locomotor activity patterns associated with these disease models. This work extends our prior demonstration that PhenoCube™ can characterize circadian dysfunction in BACHD mice and shows that this system, with the experimental protocols used, is a sensitive and efficient tool for a first pass high-throughput screening of mouse disease models in general and mouse models of neurodegeneration in particular.

Grant support

Supported by the CHDI foundation. CHDI Foundation is a not-for-profit biomedical research organization exclusively dedicated to discovering and developing therapeutics that slow the progression of Huntington’s disease. CHDI Foundation conducts research in a number of different ways; for the purposes of this manuscript, all research was conceptualized, planned, and directed by CHDI and PsychoGenics scientific staff and conducted at the contract research organization PsychoGenics, Inc. Igor Filippov, Richard Mushlin, Ahmad Paintdakhi, Liliana Menalled, Sylvie Ramboz, and Dani Brunner are all employed by PsychoGenics, Inc., a for-profit institution. The authors have declared that no further competing interests exist.