qMotor a set of rules for sensitive robust and quantitative measurements of motor performances in mice

摘要

Phenotypic analysis of mouse models of human diseases is essential to understand the underlying disease mechanisms and to develop therapeutics. Many models of neurodegenerative diseases are associated with motor dysfunction, a powerful readout for the disease. We describe here a set of measures to quantitatively monitor early disease onset and progression by rotarod analyses. We named this set of rules qMotor because it enables sensitive, robust and quantitative measurements of motor performance. Results can be obtained in three days. qMotor can be used to assess early disease onset, before paralysis, as well as disease progression in diverse mouse models and can be exploited to define robust and humane experimental endpoints, thereby reducing animal suffering. As an example application, we apply qMotor to SOD1^G93A transgenic mice. Early studies with the original transgenic SOD1^G93A mice in the hybrid background (B6SJL-Tg(SOD1-G93A) have been criticized due to high noise in this mixed background and inadequate study designs. We applied qMotor in SOD1^G93A transgenic mice in an inbred C57BL/6J background, hereafter called iSOD1^G93A, and demonstrate a remarkably robust and consistent phenotype in this line that can be used to evaluate therapeutic approaches. qMotor is a protocol generically applicable to different mouse models.