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Infection and Immunity, February 2005, p. 741-747, Vol. 73, No. 2
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.2.741-747.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Genetic Control of Bordetella pertussis Infection: Identification of Susceptibility Loci Using Recombinant Congenic Strains of Mice

H. A. Banus,1,2 H. J. van Kranen,2 F. R. Mooi,1 B. Hoebee,2 N. J. Nagelkerke,3 P. Demant,4 and T. G. Kimman1*

Laboratory for Vaccine-Preventable Diseases,1 Laboratory of Toxicology, Pathology, and Genetics,2 Computerization and Methodological Consultancy Unit, National Institute of Public Health and the Environment (RIVM), Bilthoven, The Netherlands,3 Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, New York4

Received 29 July 2004/ Returned for modification 1 September 2004/ Accepted 23 September 2004

Susceptibility to and severity of Bordetella pertussis infection in infants and children vary widely. The spectrum of clinical symptoms ranges from subclinical infection to mild disease, severe whooping cough, and death. The aims of this study were to examine genetic susceptibilities of mice to B. pertussis and to identify genetic loci in the mouse genome that are involved in susceptibility to B. pertussis infection. For this purpose we screened two sets of recombinant congenic strains (RCS) of mice, HcB and CcS, for differences in the numbers of bacteria in the lung 7 days after inoculation. For both CcS and in HcB mice, a wide range in numbers of bacteria in the lung was found, suggesting that the course of infection is under multigenic control. From both RCS sets of mice, we selected one strain to identify possible susceptibility loci in F2 hybrid mice. The degree of lung colonization 7 days postinoculation in these F2 mice was evaluated in relation to genetic markers by linkage analysis. We found three novel loci that are involved in the control of B. pertussis infection. One locus, designated B. pertussis susceptibility locus 1 (Bps-1), was identified on chromosome 12. The presence of the C57BL/10 genome on this locus instead of the C3H genome significantly decreased the number of B. pertussis bacteria in the lung. Bps-1 has a dominant-positive effect on the clearance of B. pertussis from the lung. The function of most genes in this region is unknown. Two other loci, Bps-2 and Bps-3, showed genetic interaction and are located on chromosomes 5 and 11. We aim to identify the gene(s) in these regions which modify susceptibility to B. pertussis.

* Corresponding author. Mailing address: Laboratory for Vaccine-Preventable Diseases, National Institute of Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven, The Netherlands. Phone: 31 30 2742330. Fax: 31 30 2744449. E-mail: tg.kimman{at}rivm.nl.

Editor: D. L. Burns

Infection and Immunity, February 2005, p. 741-747, Vol. 73, No. 2
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.2.741-747.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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  • Burgio, G., Szatanik, M., Guenet, J.-L., Arnau, M.-R., Panthier, J.-J., Montagutelli, X. (2007). Interspecific Recombinant Congenic Strains Between C57BL/6 and Mice of the Mus spretus Species: A Powerful Tool to Dissect Genetic Control of Complex Traits. Genetics 177: 2321-2333 [Abstract] [Full Text]  
  • Banus, S., Bottema, R. W. B., Siezen, C. L. E., Vandebriel, R. J., Reimerink, J., Mommers, M., Koppelman, G. H., Hoebee, B., Thijs, C., Postma, D. S., Kimman, T. G., Stelma, F. F. (2007). Toll-Like Receptor 4 Polymorphism Associated with the Response to Whole-Cell Pertussis Vaccination in Children from the KOALA Study. CVI 14: 1377-1380 [Abstract] [Full Text]  
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