qMotor, a set of rules for sensitive, robust and quantitative measurement of motor performance in mice

摘要

Phenotypic analysis of mouse models of human diseases is essential to understanding the underlying disease mechanisms and to developing 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. We named this set of rules qMotor because it enables sensitive, robust and quantitative measurement of motor performance in 3 d. 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 end points, thereby reducing animal suffering. As an example, 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 because of high noise in this mixed background and because of inadequate study designs. We applied qMotor in SOD1(G93A) transgenic mice in an inbred C57BL/6J background, hereafter called iSOD1(G93A) mice, and show a remarkably robust and consistent phenotype in this line that we use to evaluate a therapeutic approach. qMotor is a protocol generically applicable to different mouse models.