title: Online breath gas analysis in unrestrained mice by hs-PTR-MS.
abstract: The phenotyping of genetic mouse models for human disorders may greatly benefit from breath gas analysis as a noninvasive tool to identify metabolic alterations in mice. Phenotyping screens such as the German Mouse Clinic demand investigations in unrestrained mice. Therefore, we adapted a breath screen in which exhaled volatile organic compounds (VOCs) were online monitored by proton transfer reaction mass spectrometry (hs-PTR-MS). The source strength of VOCs was derived from the dynamics in the accumulation profile of exhaled VOCs of a single mouse in a respirometry chamber. A careful survey of the accumulation revealed alterations in the source strength due to confounders, e.g., urine and feces. Moreover changes in the source strength of humidity were triggered by changes in locomotor behavior as mice showed a typical behavioral pattern from activity to settling down in the course of subsequent accumulation profiles. We demonstrated that metabolic changes caused by a dietary intervention, e.g., after feeding a high-fat diet (HFD) a sample of 14 male mice, still resulted in a statistically significant shift in the source strength of exhaled VOCs. Applying a normalization which was derived from the distribution of the source strength of humidity and accounted for varying locomotor behaviors improved the shift. Hence, breath gas analysis may provide a noninvasive, fast access to monitor the metabolic adaptation of a mouse to alterations in energy balance due to overfeeding or fasting and dietary macronutrient composition as well as a high potential for systemic phenotyping of mouse mutants, intervention studies, and drug testing in mice.
authors.affiliation: Research Unit Medical Radiation Physics and Diagnostics, Helmholtz Zentrum München-German Research Center for Environmental Health (GmbH), 85764, Neuherberg, Germany, szymczak@helmholtz-muenchen.de.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Szymczak
authors.forename: Jan
authors.initials: J
authors.lastname: Rozman
authors.forename: Vera
authors.initials: V
authors.lastname: Höllriegl
authors.forename: Martin
authors.initials: M
authors.lastname: Kistler
authors.forename: Stefan
authors.initials: S
authors.lastname: Keller
authors.forename: Dominika
authors.initials: D
authors.lastname: Peters
authors.forename: Moritz
authors.initials: M
authors.lastname: Kneipp
authors.forename: Holger
authors.initials: H
authors.lastname: Schulz
authors.forename: Christoph
authors.initials: C
authors.lastname: Hoeschen
authors.forename: Martin
authors.initials: M
authors.lastname: Klingenspor
authors.forename: Martin Hrabě
authors.initials: MH
authors.lastname: de Angelis
mesh_terms: D000818:Animals; D001944:Breath Tests / Q000295:instrumentation / Q000379:methods*; D016000:Cluster Analysis; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000502:physiology*; D013058:Mass Spectrometry / Q000379:methods*; D053858:Metabolic Networks and Pathways / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D055549:Volatile Organic Compounds / Q000032:analysis / Q000378:metabolism*
chemical_list: D055549:Volatile Organic Compounds