On-line breath gas analysis in unrestrained mice by hs-PTR-MS 1 2

20 The phenotyping of genetic mouse models for human disorders may greatly benefit from breath gas 21 analysis as a noninvasive tool to identify metabolic alterations in mice. Phenotyping screens such as the 22 German Mouse Clinic demand investigations in unrestrained mice. Therefore, we adapted a breath screen 23 in which exhaled volatile organic compounds (VOCs) were online monitored by proton transfer reaction 24 mass spectrometry (hs-PTR-MS). The source strength of VOCs was derived from the dynamics in the 25 accumulation profile of exhaled VOCs of a single mouse in a respirometry chamber. A careful survey of 26 the accumulation revealed alterations in the source strength due to confounders, e.g., urine and feces. 27 Moreover changes in the source strength of humidity were triggered by changes in locomotor behavior 28 aSMice showed a typical behavioral pattern from activity to settling down in the course of subsequent 29 accumulation profiles. We demonstrated that metabolic changes caused by a dietary intervention, e.g., 30 after feeding a high-fat diet (HFD) a sample of 14 male mice, still resulted in a statistically significant 31 shift in the source strength of exhaled VOCs. Applying a normalization which was derived from the 32 distribution of the source strength of humidity and accounted for varying locomotor behaviors improved 33 the shift. Hence, breath gas analysis may provide a noninvasive, fast access to monitor the metabolic 34 adaptation of a mouse to alterations in energy balance due to overfeeding or fasting and dietary 35 macronutrient composition as well as a high potential for systemic phenotyping of mouse mutants, 36 intervention studies, and drug testing in mice. 37

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