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November 2001, Volume 2, Number 7, Pages 388-397
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Full Paper
Genetic control of susceptibility to experimental Lyme arthritis is polygenic and exhibits consistent linkage to multiple loci on chromosome 5 in four independent mouse crosses
R J Roper1,d, J J Weis2,b, B A McCracken1,a, C B Green1, Y Ma2, K S Weber1, D Fairbairn1, R J Butterfield1, M R Potter2,e, J F Zachary1, R W Doerge3,c and C Teuscher1,b

1Department of Veterinary Pathobiology, University of Illinois at Urbana-Champaign, Urbana, IL 61802, USA

2Department of Pathology, University of Utah, Salt Lake City, UT 84132, USA

3Departments of Agronomy and Statistics, Purdue University, West Lafayette, IN 47907, USA

Correspondence to: Dr C Teuscher, Department of Veterinary Pathobiology, 2001 South Lincoln Avenue, University of Illinois at Urbana-Champaign, Urbana, IL 61802, USA. E-mail: cteusche@uiuc.edu

aPresent address: Pet Products R&D, Ralston Purina Company, St Louis, MO 63164, USA.

bThis work was supported by NIH AR43521 (to JJW and CT).

cRWD was partially funded by USDA grant 98-35300-6173.

dRJR was partially supported by NIH Cell and Molecular Biology Training Grant T32-GM-07283.

eMRP was supported as a predoctoral trainee by NIH Genetics Training Grant T32-GM-07464.

Core facilities at the University of Utah were supported by NIH P30-CA-42014.

Abstract

C3H/He mice infected with Borrelia burgdorferi develop severe arthritis and are high antibody responders, while infected C57BL/6 and BALB/c mice develop mild arthritis and less robust humoral responses. Genetic analysis using composite interval mapping (CIM) on reciprocal backcross populations derived from C3H/HeN and C57BL/6N or C3H/HeJ and BALB/cAnN mice identified 12 new quantitative trait loci (QTL) linked to 10 murine Lyme disease phenotypes. These QTL reside on chromosomes 1, 2, 4, 6, 7, 9, 10, 12, 14, 15, 16, and 17. A reanalysis of an F2 intercross between C57BL/6N and C3H/HeN mice using CIM identified two new QTL on chromosomes 4 and 15 and confirmed the location of seven previously identified loci. Two or more experimental crosses independently verified six QTL controlling phenotypes after B. burgdorferi infection. Additionally, Bb2 on chromosome 5 was reproduced in four experimental populations and was linked to the candidate locus Cora1. Evidence of four distinct QTL residing within the 30-cM region of chromosome 5 encompassing the previously mapped Bb2 and Bb3 loci was shown by CIM. Interestingly, some alleles contributing to susceptibility to Lyme arthritis were derived from C57BL/6N and BALB/cAnN mice, showing that disease-resistant strains harbor susceptibility alleles. Genes and Immunity (2001) 2, 388-397.

Keywords

Borrelia burgdorferi; Lyme disease; arthritis; genetic control; quantitative trait loci; composite interval mapping

Received 25 May 2001; revised 10 August 2001; accepted 10 August 2001
November 2001, Volume 2, Number 7, Pages 388-397
Table of contents    Previous  Abstract  Next   Full text  PDF