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Fine Mapping of Leishmania major Susceptibility Locus lmr2 and Evidence of a Role for Fli1 in Disease and Wound Healing

Citation

Sakthianandeswaren, A and Curtis, JM and Elso, C and Kumar, B and Baldwin, TM and Lopaticki, S and Kedzierski, L and Smyth, GK and Foote, SJ and Handman, E, Fine Mapping of Leishmania major Susceptibility Locus lmr2 and Evidence of a Role for Fli1 in Disease and Wound Healing, Infection and Immunity, 78, (6) pp. 2734-2744. ISSN 0019-9567 (2010) [Refereed Article]


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Copyright Statement

Copyright © 2010, American Society for Microbiology.

DOI: doi:10.1128/IAI.00126-10

Abstract

Genetic linkage studies of the host response to Leishmania major, the causative agent of cutaneous leishmaniasis,have identified significant genetic complexity in humans and mice. In the mouse model, multiple loci have been implicated in susceptibility to infection, but to date, the genes underlying these loci have not been identified. We now describe the contribution of a novel candidate gene, Fli1, to both L. major resistance and enhanced wound healing. We have previously mapped the L. major response locus, lmr2, to proximal chromosome 9 in a genetic cross between the resistant C57BL/6 strain and the susceptible BALB/c strain. We now show that the presence of the resistant C57BL/6 lmr2 allele in susceptible BALB/c mice confers an enhanced L. major resistance and wound healing phenotype. Fine mapping of the lmr2 locus permitted the localization of the lmr2 quantitative trait locus to a 5-Mb interval comprising 21 genes, of which microarray analysis was able to identify differential expression in 1 gene—Fli1. Analysis of Fli1 expression in wounded and L. major-infected skin and naïve and infected lymph nodes validated the importance of Fli1 in lesion resolution and wound healing and identified 3 polymorphisms in the Fli1 promoter, among which a GA repeat element may be the important contributor.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Clinical Sciences
Research Field:Infectious Diseases
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Infectious Diseases
Author:Foote, SJ (Professor Simon Foote)
ID Code:64839
Year Published:2010
Web of Science® Times Cited:24
Deposited By:Menzies Institute for Medical Research
Deposited On:2010-09-07
Last Modified:2011-05-03
Downloads:0

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