Are the Lsh and Ity disease resistance genes at one locus on mouse chromosome 1?

Plant, Janet E.; Blackwell, Jenefer M.; O'Brien, A D; Bradley, David J.; Glynn, A. A.

doi:10.1038/297510a0

Cited by 133 publications

(58 citation statements)

References 6 publications

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“…Although BALB/c (Nramp1 Ϫ ) and C3H/HeN (Nramp1 ϩ ) mice vary in a number of genetic loci, a major difference in their susceptibility to Salmonella infection is in the Nramp1 gene (43). To determine whether the grvA virulence phenotype would be altered in Nramp1 ϩ mice, we competed the grvA null mutant (JS155) against wild type in i.p.…”

Section: Resultsmentioning

confidence: 99%

Characterization ofgrvA, an Antivirulence Gene on the Gifsy-2 Phage inSalmonella entericaSerovar Typhimurium

Slauch

2001

J Bacteriol

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The lambdoid phage Gifsy-2 contributes significantly to Salmonella enterica serovar Typhimurium virulence. The phage carries the periplasmic superoxide dismutase gene, sodCI, and other unidentified virulence factors. We have characterized the gene grvA, a single open reading frame inserted in the opposite orientation in the tail operon of the Gifsy-2 phage. Contrary to what is observed with classic virulence genes, grvA null mutants were more virulent than wild type as measured by intraperitoneal competition assays in mice. We have termed this effect antivirulence. Wild-type grvA in single copy complemented this phenotype. However, grvA ؉ on a multicopy plasmid also conferred the antivirulence phenotype. Neither a grvA null mutation nor the grvA ؉ plasmid conferred a growth advantage or disadvantage in laboratory media. The antivirulence phenotype conferred by the grvA null mutation and the grvA ؉ plasmid required wild-type sodCI but was independent of other virulence factors encoded on Gifsy-2. These results suggest that in a wild-type situation, GrvA decreases the pathogenicity of serovar Typhimurium in the host, most likely by affecting resistance to toxic oxygen species. These virulence phenotypes were independent of functional Gifsy-2 phage production. Our data suggest that the contribution of Gifsy-2 is a complicated sum of both positive virulence factors such as sodCI and antivirulence factors such as grvA.

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Section: Resultsmentioning

confidence: 99%

Characterization ofgrvA, an Antivirulence Gene on the Gifsy-2 Phage inSalmonella entericaSerovar Typhimurium

Slauch

2001

J Bacteriol

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“…The association reported here certainly makes biological sense. The Nramp1 gene in cattle is associated with resistance to B. abortus (15) and in the mouse with resistance to several intracellular bacteria that share with B. abortus the preference for an intracellular life (37,44). More importantly, the resistance-associated allele of the bovine Nramp1 gene, when expressed in stably transfected RAW264.7 macrophages, controls the in vitro replication of B. abortus (4).…”

Section: Discussionmentioning

confidence: 99%

“…The presence of Nramp1 in bacteria and mammals has suggested that intracellular pathogens and host cells compete for the same nutrient, each competitor attempting to steal essential cations for its own benefit (18). The mouse Nramp1 gene confers resistance to several unrelated intracellular pathogens, including Salmonella enterica serovar Typhimurium, Leishmania donovani, and Mycobacterium bovis BCG (37,44). The human Nramp1 gene confers resistance to Mycobacterium tuberculosis (6), and the cattle Nramp1 gene confers resistance to Brucella abortus (15).…”

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confidence: 99%

Genetic Resistance toBrucella abortusin the Water Buffalo (Bubalus bubalis)

Borriello

Capparelli²,

Bianco

et al. 2006

Infect Immun

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Brucellosis is a costly disease of water buffaloes (Bubalus bubalis). Latent infections and prolonged incubation of the pathogen limit the efficacy of programs based on the eradication of infected animals. We exploited genetic selection for disease resistance as an approach to the control of water buffalo brucellosis. We tested 231 water buffalo cows for the presence of anti-Brucella abortus antibodies (by the agglutination and complement fixation tests) and the Nramp1 genotype (by PCR-denaturing gradient gel electrophoresis). When the 231 animals (58 cases and 173 controls) were divided into infected (seropositive) and noninfected (seronegative) groups and the Nramp1 genotypes were compared, the seropositive subjects were 52 out of 167 (31%) in the Nramp1A ؉ (Nramp1AA or Nramp1AB) group and 6 out of 64 (9.4%) in the Nramp1A ؊ (Nramp1BB) group (odds ratio, 4.37; 95% confidence limits, 1.87 to 10.19; 2 , 11.65 for 1 degree of freedom). Monocytes from Nramp1BB subjects displayed significantly (P < 0.01) higher levels of Nramp1 mRNA than Nramp1AA subjects and also a significantly (P < 0.01) higher ability in controlling the intracellular replication of several Brucella species in vitro. Thus, selection for the Nramp1BB genotype can become a valuable tool for the control of water buffalo brucellosis in the areas where the disease is endemic.

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“…21 Linkage analysis mapped Bcg to murine chromosome 1 22 and also indicated that Bcg was the same gene as the genes determining resistance to leishmania, salmonella and other mycobacterial species such as M. lepraemurium and M. intracellulare. [23][24][25][26][27][28][29][30][31] In vivo, Bcg influences the initial phase of infection with mycobacteria but does not affect the acquired immune response. In vitro, macrophages from Bcg s strains show decreased ability to restrict the growth of mycobacteria, salmonella and leishmania.…”

Section: Nramp1mentioning

confidence: 99%

Susceptibility to mycobacterial infections: the importance of host genetics

2003

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There is substantial evidence that host genetic factors are important in determining susceptibility to mycobacteria. Several different techniques have been used to identify the genes involved. Studies of an inbred strain of mice with increased susceptibility to mycobacteria, salmonella and leishmania infections led to the identification of the natural resistance-associated macrophage protein gene (Nramp1). Case-control studies have confirmed the importance of the human equivalent of this gene, NRAMP1, and have also suggested that the major histocompatibility complex and vitamin-D receptor genes may be involved in determining human susceptibility to mycobacteria. Studies of individuals with the rare condition of increased susceptibility to disseminated bacille Calmette-Guerin and other atypical mycobacterial infections have identified several abnormalities in the genes encoding the interferon gamma receptor (IFNgR) ligand binding chain, IFNgR signal transduction chain, IFNg signal transduction and activation of transcription-1, interleukin 12 receptor b1 subunit and interleukin 12 p40 subunit. A genome-wide linkage study has been performed to identify genes exerting a major effect on tuberculosis susceptibility in the general population. Linkages were found to markers on chromosomes 15 and X. Studies to identify the genes responsible are in progress.

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Are the Lsh and Ity disease resistance genes at one locus on mouse chromosome 1?

Cited by 133 publications

References 6 publications

Characterization ofgrvA, an Antivirulence Gene on the Gifsy-2 Phage inSalmonella entericaSerovar Typhimurium

Characterization ofgrvA, an Antivirulence Gene on the Gifsy-2 Phage inSalmonella entericaSerovar Typhimurium

Genetic Resistance toBrucella abortusin the Water Buffalo (Bubalus bubalis)

Susceptibility to mycobacterial infections: the importance of host genetics

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