RT Journal Article
SR Electronic
T1 Early Detection of Apathetic Phenotypes in Huntington’s Disease Knock-in Mice Using Open Source Tools
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 208520
DO 10.1101/208520
A1 Shawn Minnig
A1 Robert M. Bragg
A1 Hardeep S. Tiwana
A1 Wes T. Solem
A1 William S. Hovander
A1 Eva-Mari S. Vik
A1 Madeline Hamilton
A1 Samuel R. W. Legg
A1 Dominic D. Shuttleworth
A1 Sydney R. Coffey
A1 Jeffrey P. Cantle
A1 Jeffrey B. Carroll
YR 2017
UL http://biorxiv.org/content/early/2017/10/25/208520.abstract
AB Apathy is one of the most prevalent and progressive psychiatric symptom in Huntington’s disease (HD) patients. However, preclinical work in HD mouse models tend to focus on molecular and motor, rather than affective, phenotypes. Measuring behavior in mice often produces noisy data and requires large cohorts to detect phenotypic rescue with appropriate power. The operant equipment necessary for measuring affective phenotypes is typically expensive, proprietary to commercial entities, and bulky which can render adequately sized mouse cohorts as cost-prohibitive. Thus, we describe here a home-built open-source alternative to commercial hardware that is reliable, scalable, and reproducible. Using off-the-shelf hardware, we adapted and built several of the rodent operant buckets (ROBucket) designed to test HttQ111/+ mice for attention deficits in fixed ratio (FR) and progressive ratio (PR) tasks. We find that, despite normal performance in reward attainment in the FR task, HttQ111/+ mice exhibit reduced PR performance at 9-11 months of age, suggesting motivational deficits. We replicated this in two independent cohorts, which demonstrates the reliability and utility of both the apathetic phenotype, and these ROBuckets, for preclinical HD studies.