Novel approaches to assess therapeutic efficacy in the MRL/lpr model of lupus

Abstract

Abstract Spontaneous genetic models of systemic lupus erythematosus (SLE), such as MRL/lpr and NZB/W F1 mice, are commonly used to assess therapeutic efficacy. Therapies are evaluated against several reliable standard measures, including proteinuria, anti-dsDNA, skin lesions, splenomegaly, nephritis, and survival. We hypothesize that continuous monitoring of behavioral and physiologic parameters will provide additional meaningful data to assess disease and efficacy. Here, we treated MRL/lpr mice with two reference compounds, cyclophosphamide (CP: 25mg/kg, IP, weekly) and dexamethasone (DEX: 2mg/kg, IP, 3× week). Throughout the experiment, mice were housed in Vium’s Digital Vivarium, which provides continuous monitoring and assessment of behavioral and physiologic measures using a network of cameras and sensors. Digital metrics and standard measures were displayed and analyzed in near real-time, through an online interface. Group disease profiles were compared using automatically generated breathing rate and motion metrics, in addition to standard measures. Proteinuria, body weight, and spleen size showed disease establishment in MRL/lpr mice as early as 16 weeks of age, which was ameliorated by CP or DEX (p’s < 0.03). Breathing rate significantly increased in MRL/lpr vehicle-treated mice as early as 13 weeks of age, while nighttime motion significantly decreased in MRL/lpr vehicle-treated mice by 14 weeks. Changes in breathing rate and motion detected in MRL/lpr mice were rescued by administration of CP or DEX (p’s < 0.0001). Our results demonstrate that continuous measurement of breathing rate and motion are useful additional measures for evaluating disease severity and therapeutic efficacy in the MRL/lpr murine model of SLE.