Characterization of candidate genes regulating the severity of lyme disease

Update item information
Publication Type dissertation
School or College School of Medicine
Department Pathology
Author Potter, Melissa R.
Title Characterization of candidate genes regulating the severity of lyme disease
Date 2001-12
Description A genetic mapping study was performed to identify segments of the mouse genome responsible for control of arthritis development during Borrelia burgdorferi infection. Multiple quantitative trait loci were identified using composite interval mapping of an F2 intercross population of C3H/HeN and C57BL/6N mice and reciprocal backcross populations derived from C3H/HeN and C57BL/6N or C3H/HeJ and BALB/cAnN mice. Four arthritis severity loci were identified on Chromosome 5. Suggestive linkage to a cluster of genes on mouse chromosome 11, including IL-4 and IL-13, was also identified. The literature provides conflicting reports regarding the role of IL-4 in Lyme disease. Therefore, the importance of IL-4 and IL-13 regulation of Lyme disease was examined in C57BL/6J and BALB/cJ mice with targeted disruptions in IL-4, IL-4Ralpha or both. IL-4 and IL-13 have been eliminated as candidate genes controlling the development of severe Lyme disease as neither arthritis severity nor bacterial load was altered in any B. burgdorferi infected, knock-out mice. Furthermore, IgG1 antibodies are not required for host control of bacterial numbers. Osteopontin falls within an arthritis severity locus identified on chromosome 5 and was chosen for further examination. Osteopontin regulates cytokine production, host control of pathogens, and maintenance and remodeling of tissue during inflammation. Its alleles are polymorphic between the C3H and C57BL/6 strains. The importance of osteopontin in Lyme disease was examined using osteopontin deficient mice on both an inbred 129S and mixed C57BL/6J X 129S backgrounds. Arthritis severity was similar in osteopontin-deficient and wild-type mice on the 129S background; therefore osteopontin is not required for resistance to severe Lyme arthritis. Arthritis was more severe in some mice on the osteopontin-deficient C57BL/6J X 129S mixed backgrounds. This increase in severity is most likely due to background effects, not the osteopontin deficiency. Further, host control of spirochete numbers is not regulated by osteopontin, as all osteopontin-deficient mice harbored numbers of bacteria similar to their wild-type littermates..
Type Text
Publisher University of Utah
Subject Borrelia burgdorferi Group; Osteopontin
Subject MESH Lyme Disease; Genetics
Dissertation Institution University of Utah
Dissertation Name PhD
Language eng
Relation is Version of Digital reproduction of "Characterization of candidate genes regulating the severity of lyme disease." Spencer S. Eccles Health Sciences Library. Print version of "Characterization of candidate genes regulating the severity of lyme disease." available at J. Willard Marriott Library Special Collection. RC39.5 2001 .P68.
Rights Management © Melissa R. Potter.
Format Medium application/pdf
Format Extent 3,153,216 bytes
Identifier undthes,5187
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available).
Funding/Fellowship NIH AR43521 to Janis J. Weis and Cory Teuscher, Predoctoral trainee by the NIH Genetics Training Grant T32-GM-07464.
Master File Extent 3,153,239 bytes
ARK ark:/87278/s6zp47xm
Setname ir_etd
Date Created 2012-04-24
Date Modified 2012-04-24
ID 190909
Reference URL