Clinical Chemistry of Congenic Mice with Quantitative Trait Loci for Predicted Responses to Trypanosoma congolense Infection

Author:

Rathkolb Birgit12,Noyes Harry A.3,Brass Andy45,Dark Paul6,Fuchs Helmut1,Gailus-Durner Valérie1,Gibson John7,de Angelis Martin Hrabé18,Ogugo Moses7,Iraqi Fuad7,Kemp Steve J.73,Naessens Jan7,Pope Mathew E.7,Wolf Eckhard2,Agaba Morris7

Affiliation:

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. School of Biological Sciences, University of Liverpool, Crown Street, Liverpool L69 7ZB, United Kingdom

4. Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, United Kingdom

5. School of Computer Science, Kilburn Building, University of Manchester, Oxford Road, Manchester M13 9PL, United Kingdom

6. Intensive Care Medicine, Salford Royal NHS Foundation Trust, The University of Manchester, Manchester M6 8HD, United Kingdom

7. International Livestock Research Institute, P.O. Box 30709, Nairobi 00100, Kenya

8. Experimental Genetics, Center of Life and Food Sciences Weihenstephan, Technische Universität München, Alte Akademie 8, D 85354 Freising, Germany

Abstract

ABSTRACT 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.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Immunology,Microbiology,Parasitology

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