Document Detail


Genetic control of susceptibility to infection with Mycobacterium tuberculosis in mice.
MedLine Citation:
PMID:  11197687     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Genetic factors play a key role in host response, disease severity, and ultimate outcome of infection with Mycobacterium tuberculosis in humans. In the mouse, the DBA/2J strain is very susceptible to M. tuberculosis H37Rv infection, while the C57Bl/6J strain is resistant. In DBA/2J, a heavier bacterial burden causes a unique phenotype, that includes very severe and rapidly fatal pulmonary disease with extensive exudation of neutrophils and tissue necrosis, as opposed to slower progressive pulmonary disease characterized by the accumulation of epithelioid macrophages with protective immune and inflammatory responses in C57Bl/6J. To identify the genes responsible for differences in host response to M. tuberculosis in these two strains, 95 animals of an informative (C57Bl/6J x DBA/2J) F2 cross were infected intravenously with M. tuberculosis (1 x 10(5) CFU) and duration of survival was used as a quantitative phenotypic measure of susceptibility in a whole genome scan. Quantitative trait locus analysis (QTL) showed that the genetically controlled susceptibility was multigenic. QTL analysis identified two significant linkages on the distal portion of chromosome 1 (Trl-1, LOD, 4.80) and on the proximal portion of chromosome 7 (Trl-3, LOD, 4.66) that each account for approximately 21% of the phenotypic variance. A third suggestive linkage was identified on the proximal portion of chromosome 3 (Trl-2, LOD, 3.93; additional 18% of the variance). At each locus, homozygosity for the parental C57Bl/6J alleles was associated with increased resistance to infection. These novel mouse loci provide the basis for evaluating a possible association of the corresponding syntenic chromosomal regions in humans with susceptibility to tuberculosis.
Authors:
L M Mitsos; L R Cardon; A Fortin; L Ryan; R LaCourse; R J North; P Gros
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Genes and immunity     Volume:  1     ISSN:  1466-4879     ISO Abbreviation:  Genes Immun.     Publication Date:  2000 Dec 
Date Detail:
Created Date:  2001-01-29     Completed Date:  2001-04-26     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  100953417     Medline TA:  Genes Immun     Country:  England    
Other Details:
Languages:  eng     Pagination:  467-77     Citation Subset:  IM    
Affiliation:
Department of Biochemistry and Center for Host Resistance, McGill University, Montreal, Canada.
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MeSH Terms
Descriptor/Qualifier:
Animals
Female
Genetic Predisposition to Disease / genetics*
Male
Mice
Mice, Inbred C57BL
Mice, Inbred DBA
Mycobacterium tuberculosis / immunology
Tuberculosis / genetics*,  immunology
Grant Support
ID/Acronym/Agency:
AI-37844/AI/NIAID NIH HHS; HL-64565/HL/NHLBI NIH HHS; R01 AI 35237/AI/NIAID NIH HHS

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