Advertisement

Mammalian Genome

, Volume 25, Issue 3–4, pp 129–140 | Cite as

Online breath gas analysis in unrestrained mice by hs-PTR-MS

  • Wilfried Szymczak
  • Jan Rozman
  • Vera Höllriegl
  • Martin Kistler
  • Stefan Keller
  • Dominika Peters
  • Moritz Kneipp
  • Holger Schulz
  • Christoph Hoeschen
  • Martin Klingenspor
  • Martin Hrabě de Angelis
Article

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.

Keywords

Drift Tube Source Strength Methanethiol Accumulation Profile Proton Transfer Reaction Mass Spectrometry 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

The studies were supported by the grants from the German Federal Ministry of Education and Research (NGFN-Plus, Grant Nos.: 01GS0850, 01GS0869, and Infrafrontier Grant No. 01KX1012). They were also supported by funding from the German Federal Ministry of Education and Research (BMBF) granted to the German Center for Diabetes Research (DZD e.V.).

References

  1. Aprea E, Morisco F, Biasioli F, Vitaglione P, Cappellin L, Soukoulis C, Lembo V, Gasperi F, D’Argenio G, Fogliano V, Caporaso N (2012) Analysis of breath by proton transfer reaction time of flight mass spectrometry in rats with steatohepatitis induced by high-fat diet. J Mass Spectrom 47:1098–1103PubMedCrossRefGoogle Scholar
  2. Bajtarevic A, Ager C, Pienz M, Klieber M, Schwarz K, Ligor M, Ligor T, Filipiak W, Denz H, Fiegl M, Hilbe W, Weiss W, Lukas P, Jamnig H, Hackl M, Haidenberger A, Buszewski B, Miekisch W, Schubert J, Amann A (2009) Noninvasive detection of lung cancer by analysis of exhaled breath. BMC Cancer 9:348PubMedCentralPubMedCrossRefGoogle Scholar
  3. Bates JHT, Irvin C (2003) Measuring lung function in mice: the phenotyping uncertainty principle. J Appl Physiol 94:1297–1306PubMedGoogle Scholar
  4. Cani PD, Delzenne NM (2009) Interplay between obesity and associated metabolic disorders: new insights into the gut microbiota. Curr Opin Pharmacol 9:737–743PubMedCrossRefGoogle Scholar
  5. Cao W, Duan Y (2007) Current status of methods and techniques for breath analysis. Crit Rev Anal Chem 37:3–13CrossRefGoogle Scholar
  6. Cope K, Risby T, Diehl AM (2000) Increased gastrointestinal ethanol production in obese mice: implications for fatty liver disease pathogenesis. Gastroenterology 119:1340–1347PubMedCrossRefGoogle Scholar
  7. Drorbaugh JE, Fenn WO (1955) A barometric method for measuring ventilation in newborn infants. Pediatrics 16:81–87PubMedGoogle Scholar
  8. Friedrich M, Petzke KJ, Raederstorff D, Wolfram S, Klaus S (2011) Acute effects of epigallocatechin gallate from green tea on oxidation and tissue incorporation of dietary lipids in mice fed a high-fat diet. Int J Obes 36(5):735–743CrossRefGoogle Scholar
  9. Fuchs H, Gailus-Durner V, Adler T, Pimentel JA, Becker L, Bolle I, Brielmeier M, Calzada-Wack J, Dalke C, Ehrhardt N, Fasnacht N, Ferwagner B, Frischmann U, Hans W, Holter SM, Holzlwimmer G, Horsch M, Javaheri A, Kallnik M, Kling E, Lengger C, Maier H, Mossbrugger I, Morth C, Naton B, Noth U, Pasche B, Prehn C, Przemeck G, Puk O, Racz I, Rathkolb B, Rozman J, Schable K, Schreiner R, Schrewe A, Sina C, Steinkamp R, Thiele F, Willershauser M, Zeh R, Adamski J, Busch DH, Beckers J, Behrendt H, Daniel H, Esposito I, Favor J, Graw J, Heldmaier G, Hofler H, Ivandic B, Katus H, Klingenspor M, Klopstock T, Lengeling A, Mempel M, Muller W, Neschen S, Ollert M, Quintanilla-Martinez L, Rosenstiel P, Schmidt J, Schreiber S, Schughart K, Schulz H, Wolf E, Wurst W, Zimmer A, Hrabe de Angelis M (2009) The German Mouse Clinic: a platform for systemic phenotype analysis of mouse models. Curr Pharm Biotechnol 10:236–243PubMedCrossRefGoogle Scholar
  10. Hansel A, Jordan A, Warneke C, Holzinger R, Lindinger W (1998) Improved detection limit of the proton-transfer reaction mass spectrometer: on-line monitoring of volatile organic compounds at mixing ratios of a few pptv. Rapid Commun Mass Spectrom 12:871–875CrossRefGoogle Scholar
  11. Hrabé de Angelis M, Strievens M (2001) Large-scale production of mouse phenotype: the search for animal models for inherited diseases in humans. Brief Bioinformatics 2:170–180PubMedCrossRefGoogle Scholar
  12. Isken F, Klaus S, Petzke KJ, Loddenkemper C, Pfeiffer AFH, Weickert MO (2010) Impairment of fat oxidation under high-vs. low glycemic index diet occurs before the development of an obese phenotype. Am J Physiol Endocrinol Metab 298:E287–E295PubMedCrossRefGoogle Scholar
  13. Jordan A, Haidacher S, Hanel G, Hartungen E, Mark L, Seehauser H, Schottkowsky R, Sulzer P, Mark TD (2009) A high resolution and high sensitivity proton-transfer-reaction time-of-flight mass spectrometer (PTR–TOF-MS). Int J Mass Spectrom 286:122–128CrossRefGoogle Scholar
  14. Keck L, Hoeschen C, Oeh U (2008) Effects of carbon dioxide in breath gas on proton transfer reaction-mass spectrometry (PTR-MS) measurements. Int J Mass Spectrom 270:156–165CrossRefGoogle Scholar
  15. Lindinger W, Hansel A, Jordan A (1998) On-line monitoring of volatile organic compounds at pptv levels by means of proton-transfer-reaction mass spectrometry (PTR-MS) medical applications, food control and environmental research. Int J Mass Spectrom Ion Process 173:191–241CrossRefGoogle Scholar
  16. Miekisch W, Schubert JK, Noeldge-Schomburg GFE (2004) Diagnostic potential of breath analysis—focus on volatile organic compounds. Clin Chim Acta 347:25–39PubMedCrossRefGoogle Scholar
  17. Nicklas W, Baneux P, Boot R, Decelle T, Deeny AA, Fumanelli M, Illgen-Wilcke B, Monitoring FWGH (2002) Recommendations for the health monitoring of rodent and rabbit colonies in breeding and experimental units. Lab Anim 36:20–42PubMedCrossRefGoogle Scholar
  18. Phillips M, Gleeson K, Hughes JMB, Greenberg J, Cataneo RN, Baker L, McVay WP (1999a) Volatile organic compounds in breath as markers of lung cancer: a cross sectional study. Lancet 353:1930–1933PubMedCrossRefGoogle Scholar
  19. Phillips M, Herrerab J, Krishnanb S, Zainb M, Greenberg J, Cataneo RN (1999b) Variation in volatile organic compounds in the breath of normal humans. J Chromatogr 729:75–88CrossRefGoogle Scholar
  20. Reinhard C, Eder G, Fuchs H, Ziesenis A, Heyder J, Schulz H (2002) Inbred strain variation in lung function. Mamm Genome 13:429–437PubMedCrossRefGoogle Scholar
  21. Riely CA, Cohen G, Lieberman M (1974) Ethane Evolution: a new index of lipid peroxidation. Science 183:208–210PubMedCrossRefGoogle Scholar
  22. Risby TH, Jiang L, Stoll S, Ingram D, Spangler E, Heim J, Cutler R, Roth GS, Rifkind JM (1999) Breath ethane as a marker of reactive oxygen species during manipulation of diet and oxygen tension in rats. J Appl Physiol 86:617–622PubMedGoogle Scholar
  23. Samuel BS, Shaito A, Motoike T, Rey FE, Backhed F, Manchester JK, Hammer RE, Williams SC, Crowley J, Yanagisawa M, Gordon JI (2008) Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. PNAS 105:16767–16772PubMedCentralPubMedCrossRefGoogle Scholar
  24. Schaefer ML, Wongravee K, Holmboe ME, Heinrich NM, Dixon SJ, Zeskind JE, Kulaga HM, Brereton RG, Reed RR, Trevejo JM (2010) Mouse urinary biomarkers provide signatures of maturation, diet, stress level, and diurnal rhythm. Chem Senses 35:459–471PubMedCentralPubMedCrossRefGoogle Scholar
  25. Schwarz K, Filipiak W, Amann A (2009) Determining concentration patterns of volatile compounds in exhaled breath by PTR-MS. J Breath Res 3:027002PubMedCrossRefGoogle Scholar
  26. Schwende FJ, Wiesler D, Jorgenson JW, Carmack M, Novotny M (1986) Urinary volatile constituents of the house mouse, Mus musculus, and their endocrine dependency. J Chem Ecol 12:277–296PubMedCrossRefGoogle Scholar
  27. Smith D, Turner C, Spanel P (2007) Volatile metabolites in the exhaled breath of healthy volunteers: their levels and distributions. J Breath Res 1:014004PubMedCrossRefGoogle Scholar
  28. Tilg H, Kaser A (2011) Gut microbiome, obesity, and metabolic dysfunction. J Clin Investig 121:2126–2132PubMedCentralPubMedCrossRefGoogle Scholar
  29. Vautz W, Nolte J, Bufe A, Baumbach JI, Peters M (2010) Analyses of mouse breath with ion mobility spectrometry: a feasibility study. J Appl Physiol 108:697–704PubMedCrossRefGoogle Scholar
  30. Vrieze A, Holleman F, Serlie MJ, Ackermans MT, Dallinga-Thie GM, Groen AK, van Nood E, Bartelsman JFW, Oozeer R, Zoetendal E, de Vos WM, Hoekstra JBL, Nieuwdorp M (2010) Metabolic effects of transplanting gut microbiota from lean donors to subjects with metabolic syndrome. Diabetologia 53:S44CrossRefGoogle Scholar
  31. Whittle CL, Fakharzadeh S, Eades J, Preti G (2007) Human breath odors and their use in diagnosis. Ann N Y Acad Sci 1098:252–266PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Wilfried Szymczak
    • 1
  • Jan Rozman
    • 2
    • 3
    • 6
  • Vera Höllriegl
    • 1
  • Martin Kistler
    • 2
  • Stefan Keller
    • 1
  • Dominika Peters
    • 1
    • 2
  • Moritz Kneipp
    • 1
  • Holger Schulz
    • 4
  • Christoph Hoeschen
    • 1
  • Martin Klingenspor
    • 3
  • Martin Hrabě de Angelis
    • 2
    • 5
    • 6
  1. 1.Research Unit Medical Radiation Physics and DiagnosticsHelmholtz Zentrum München-German Research Center for Environmental Health (GmbH)NeuherbergGermany
  2. 2.German Mouse Clinic, Institute of Experimental GeneticsHelmholtz Zentrum München-German Research Center for Environmental Health (GmbH)NeuherbergGermany
  3. 3.ZIEL Department of Molecular Nutritional Medicine, Else Kröner-Fresenius CenterTechnische Universität MünchenFreisingGermany
  4. 4.Institute of Epidemiology IHelmholtz Zentrum München-German Research Center for Environmental Health (GmbH)NeuherbergGermany
  5. 5.Center of Life and Food Sciences WeihenstephanTechnische Universität MünchenFreisingGermany
  6. 6.German Center for Diabetes Research (DZD)NeuherbergGermany

Personalised recommendations