Transcriptomics

Dataset Information

19

Genetic Determinants for Susceptibility to Staphylococcus aureus Infection in A/J and C57BL/6J


ABSTRACT: Although it has recently been shown that A/J mice are highly susceptible to Staphylococcus aureus sepsis as compared to C57BL/6J, the specific genes responsible for this differential phenotype are unknown. Using chromosome substitution strains (CSS), we found that factors on chromosomes (chr) 8, 11, and 18 are responsible for susceptibility to S. aureus sepsis in A/J mice. F1 mice from C57BL/6J X CSS8 cross (C8A) and C57BL/6J X CSS18 (C18A) were also susceptible to S. aureus (median survival < 48 h), whereas F1 mice from C57BL/6J X CSS11 cross (C11A) were resistant (median survival > 120 h) to S. aureus. Bacterial loads in the kidney were consistent with F1 median survivals, with higher bacterial counts in susceptible mice. No sexlinked associations with susceptibility were noted in F1 intercrosses. Using whole genome transcription profiling, we identified a total of 192 genes on chromosomes 8, 11, and 18 which are differentially expressed between A/J and C57BL/6J in the setting of S. aureus infection. Of these, 28 genes had Gene Ontology annotations indicating a potential immune response function. These 28 genes are associated with susceptibility to S. aureus in A/J mice, and are potential determinants of susceptibility to S. aureus infection in humans. To identify genes for which differential expression between A/J and C57BL/6J mice could contribute to host susceptibility to S. aureus infection, we compared the gene expression profiles between uninfected A/J and C57BL/6J mice and between infected A/J and C57BL/6J mice at 2, 4, 6, and 12 hours after infection.

ORGANISM(S): Mus musculus  

SUBMITTER: SunHee Ahn   Lindsay Cowell  Lindsay G Cowell 

PROVIDER: E-GEOD-19668 | ArrayExpress | 2010-08-01

SECONDARY ACCESSION(S): GSE19668PRJNA122487

REPOSITORIES: GEO, ArrayExpress

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Publications

Two genes on A/J chromosome 18 are associated with susceptibility to Staphylococcus aureus infection by combined microarray and QTL analyses.

Ahn Sun-Hee SH   Deshmukh Hitesh H   Johnson Nicole N   Cowell Lindsay G LG   Rude Thomas H TH   Scott William K WK   Nelson Charlotte L CL   Zaas Aimee K AK   Marchuk Douglas A DA   Keum Sehoon S   Lamlertthon Supaporn S   Sharma-Kuinkel Batu K BK   Sempowski Gregory D GD   Fowler Vance G VG  

PLoS pathogens 20100902 9


Although it has recently been shown that A/J mice are highly susceptible to Staphylococcus aureus sepsis as compared to C57BL/6J, the specific genes responsible for this differential phenotype are unknown. Using chromosome substitution strains (CSS), we found that loci on chromosomes 8, 11, and 18 influence susceptibility to S. aureus sepsis in A/J mice. We then used two candidate gene selection strategies to identify genes on these three chromosomes associated with S. aureus susceptibility, and  ...[more]

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