Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling time series of kidney, liver and spleen from three strains of mice infected with Trypanosoma congolense to investigate strain differences in susceptibility

ABSTRACT: In this experiment, mice from 3 strains A/J, Balb C and C57Bl6 were infected with Trypanosoma Congolense, IL1180 clone, African sleeping sickness, a disease which affects cattle in sub-saharan Africa. These mouse strains were chosen because they are a model for tolerance to infection in cattle, with A/J and Balb B being highly susceptible, and C57Bl6 being somewhat more tolerant to infection. Three tissues Kidney Liver and Spleen were harvested from cohorts at various timepoints: 0 (naive), 3, 7, 9 and 17 days post infection. Each condition thus comprises: Time, Tissue, Strain. For each condition, RNA extracts from individuals were pooled (5 per pool) prior to hybridisation.

ORGANISM(S): Mus musculus

SUBMITTER: Helen Hulme

PROVIDER: E-MEXP-1190 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

A systematic strategy for large-scale analysis of genotype phenotype correlations: identification of candidate genes involved in African trypanosomiasis.

Fisher Paul P Hedeler Cornelia C Wolstencroft Katherine K Hulme Helen H Noyes Harry H Kemp Stephen S Stevens Robert R Brass Andrew A

Nucleic acids research 20070820 16

It is increasingly common to combine Microarray and Quantitative Trait Loci data to aid the search for candidate genes responsible for phenotypic variation. Workflows provide a means of systematically processing these large datasets and also represent a framework for the re-use and the explicit declaration of experimental methods. In this article, we highlight the issues facing the manual analysis of microarray and QTL data for the discovery of candidate genes underlying complex phenotypes. We s ...[more]

PMID: 17709344

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Project description:The definition of biomarkers correlating with disease progression could have impact on the rational design of novel diagnostic approaches for bovine tuberculosis in cattle. We have used the advantages of the murine model to identify promising candidates in the host transcriptome post-infection. RNA from BALB/c splenocytes and lung cells after aerogenic Mycobacterium bovis infection were with high-density microarrays to defining biomarkers of disease progression. In antigen-stimulated splenocytes we found statically significant modulation of 1109 genes early after infection and 1134 at later time-point post-infection. 618 of these genes were modulated at both time points. In the lung 282 genes were significantly modulated post-infection. Amongst the most strongly up-regulated genes were granzyme A in spleen, and cxcl9, granzyme B, interleukin-22, interluekin-17A receptor, and ccr6 in lungs. The expression of 20 of the most up-regulated genes identified in the murine studies were evaluated using PBMC from uninfected and naturally infected cattle. We could show that the expression of cxcl9, granzyme A and interleukin-22 following in vitro stimulation with PPD was significantly increased in infected cows compared to naïve animals. Thus, we have demonstrated that murine transcriptome analysis can be used to predict responses in cattle. In addition, we have prioritised CXCL9, GnzA and IL-22 as potential additional readout systems for the ante-mortem diagnosis of bovine tuberculosis. Two groups of 5 BALB/c mice each were infecetd with approx 600 CFU M. bovis via the intranasal route. At days 3 and 14 post challenge five mice per group were euthanized and spleens and lungs harvested. One group of 5 mice were used as a control. Their splenocytes and lung cells were stimulated in vitro for 3 days with M7 protein pool. Antigen cell culture stimulations in mice were performed using an equal pool of seven secreted, immunogenic recombinant mycobacterial proteins (Rv1886c, Rv3019c, Rv3763, Rv3804c, Rv0251, Rv0287 and Rv0288) common to M. bovis and BCG, referred here as M7 protein cocktail. Each protein was used at final concentration of 2μg/ml in 3-day culture.

Dataset Information

Transcription profiling time series of kidney, liver and spleen from three strains of mice infected with Trypanosoma congolense to investigate strain differences in susceptibility

Publications

A systematic strategy for large-scale analysis of genotype phenotype correlations: identification of candidate genes involved in African trypanosomiasis.

Similar Datasets

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