Document Detail


Fine mapping of Leishmania major susceptibility Locus lmr2 and evidence of a role for Fli1 in disease and wound healing.
MedLine Citation:
PMID:  20368343     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Anuratha Sakthianandeswaren; Joan M Curtis; Colleen Elso; Beena Kumar; Tracey M Baldwin; Sash Lopaticki; Lukasz Kedzierski; Gordon K Smyth; Simon J Foote; Emanuela Handman
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-04-05
Journal Detail:
Title:  Infection and immunity     Volume:  78     ISSN:  1098-5522     ISO Abbreviation:  Infect. Immun.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-20     Completed Date:  2010-06-01     Revised Date:  2011-03-03    
Medline Journal Info:
Nlm Unique ID:  0246127     Medline TA:  Infect Immun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2734-44     Citation Subset:  IM    
Affiliation:
Ludwig Institute for Cancer Research, PO Box 2008, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia. Anu.Sakthianandeswaren@ludwig.edu.au
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MeSH Terms
Descriptor/Qualifier:
Animals
Chromosome Mapping
Crosses, Genetic
Female
Gene Expression Profiling
Genetic Loci
Genetic Predisposition to Disease*
Leishmania major / immunology*
Leishmaniasis, Cutaneous / immunology*
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Polymorphism, Genetic
Promoter Regions, Genetic
Proto-Oncogene Protein c-fli-1 / physiology*
Wound Healing*
Chemical
Reg. No./Substance:
0/Fli1 protein, mouse; 0/Proto-Oncogene Protein c-fli-1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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