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Infection and Immunity, September 2009, p. 3948-3957, Vol. 77, No. 9
0019-9567/09/$08.00+0     doi:10.1128/IAI.00658-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Clinical Chemistry of Congenic Mice with Quantitative Trait Loci for Predicted Responses to Trypanosoma congolense Infection{triangledown} ,{dagger}

Birgit Rathkolb,2,3,{ddagger} Harry A. Noyes,7,{ddagger} Andy Brass,4,5 Paul Dark,6 Helmut Fuchs,2 Valérie Gailus-Durner,2 John Gibson,1,§ Martin Hrabé de Angelis,2,8 Moses Ogugo,1 Fuad Iraqi,1,¶ Steve J. Kemp,1,7 Jan Naessens,1 Mathew E. Pope,1,|| Eckhard Wolf,3 and Morris Agaba1*

International Livestock Research Institute, P.O. Box 30709, Nairobi 00100, Kenya,1 Institute of Experimental Genetics, Helmholtz Zentrum München, Ingolstädter Landstraße 1, D-85764 Neuherberg, Germany,2 Molecular Animal Breeding and Biotechnology, and Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, Ludwig Maximilians Universität München, Feodor-Lynen-Str. 25, D-81377 Munich, Germany,3 Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, United Kingdom,4 School of Computer Science, Kilburn Building, University of Manchester, Oxford Road, Manchester M13 9PL, United Kingdom,5 Intensive Care Medicine, Salford Royal NHS Foundation Trust, The University of Manchester, Manchester M6 8HD, United Kingdom,6 School of Biological Sciences, University of Liverpool, Crown Street, Liverpool L69 7ZB, United Kingdom,7 Experimental Genetics, Center of Life and Food Sciences Weihenstephan, Technische Universität München, Alte Akademie 8, D 85354 Freising, Germany8

Received 10 June 2009/ Returned for modification 18 June 2009/ Accepted 2 July 2009

Trypanosoma congolense is a protozoan parasite that causes severe diseases in livestock. Three major quantative trait loci (QTL), Tir1, Tir2, and Tir3, control the survival time of mice after infection with T. congolense. Congenic mice carrying the C57BL/6 resistance alleles on the A/J background were developed for each of these loci. The congenic mice were used to physically map the regions containing the QTL gene(s) and to investigate the physiological effect of each locus. Clinical chemistry data for infected A/J, C57BL/6, and BALB/c mice were obtained for 15 analytes at five time points. Congenic mice were assessed for survival, parasitemia, and anemia as well as seven clinical-chemical analytes. The survival times were significantly increased in the Tir1 and Tir2 mice but not Tir3 congenic mice. The survival time of the parental inbred mice correlated negatively with parasitemia but positively with alanine aminotransferase activities in serum, suggesting that inflammatory reactions in the liver had a beneficial effect possibly associated with reduced parasitemia. However, there was no difference in parasitemia or liver enzyme activities of Tir1 and Tir2 congenic mice relative to their controls, showing that survival, parasitemia, and degree of liver damage are not associated with each other, despite the correlation in the parental lines. These data suggest that the congenic loci affect survival but do not affect control of parasite number. They may therefore act by limiting the pathological consequences of T. congolense infection.

* Corresponding author. Mailing address: International Livestock Research Institute, P.O. Box 30709, Nairobi, GPO 00100, Kenya. Phone: 254 20 422 3327. Fax: 254 20 422 3001. E-mail: m.agaba{at}cgiar.org

{triangledown} Published ahead of print on 13 July 2009.

{dagger} Supplemental material for this article may be found at http://iai.asm.org/.

Editor: W. A. Petri, Jr.

{ddagger} B.R. and H.A.N. contributed equally to this work.

§ Present address: Institute for Bioinformatics and Genetics, University of New England, Armidale, New South Wales, Australia.

Present address: Department of Human Microbiology, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel.

|| Present address: Pearson Laboratory, Petch Building, Ring Road, University of Victoria, Victoria, British Columbia V8W 3P6, Canada.

Infection and Immunity, September 2009, p. 3948-3957, Vol. 77, No. 9
0019-9567/09/$08.00+0     doi:10.1128/IAI.00658-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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