BioProject

Examination of host genome-wide changes upon encounters with pathogens provides insight into the pathogenesis of infection and disease. When performed comparatively, it may shed light on the mechanisms underlying host susceptibility. In this study, gene expression in the mouse colon was investigated in two cognate lines of mice that differ in their response to Citrobacter rodentium infection; susceptible inbred FVB/N (FVB) and resistant outbred Swiss Webster (SW) mice. Gene expression in the distal colon was investigated prior to infection and at 4 and 9 days post-inoculation using a whole mouse genome Affymetrix array. Computational analysis identified 462 (1%) probe sets differentially expressed by more than 2-fold between uninoculated SW and FVB mice. In response to C. rodentium infection, 5,123 probe sets (11.4%) were significantly modulated in one or both lines of mice. Microarray data were validated by quantitative real time RT-PCR on 35 selected genes (r = 0.87, p < 0.001) and were found to have a 94% concordance. Transcripts represented by 1,547 probe sets (3.4%), were differentially expressed between FVB and SW mice regardless of infection status (host effect). Genes associated with transport were over-represented to a greater extent than immune response-related genes (25% vs. 11% of enrichment, respectively). Electrolyte analysis revealed hypochloremia and hyponatremia in susceptible animals. The results support the hypothesis that mortality in C. rodentium-infected FVB mice is associated with impaired ion transport and development of fatal hypovolemia. These studies contribute to our understanding of the pathogenesis of C. rodentium and suggest novel strategies for the prevention and treatment of diarrhea associated with bacterial infections of the intestinal tract. Keywords: temporal change (post infection) Overall design: Global gene expression analysis was performed on the distal colon with 2-3 mice per group. Because no difference for any parameters was observed in uninfected mice at 4 or 9 dpi, the animals were pooled into an uninoculated control groups for each line of mouse. The selection of representative samples for microarray analysis was based on known infection status and colonic lesions. The final number of biological replicates for each condition was n = 5 for uninoculated FVB mice (“Fp” group), n = 4 for uninoculated SW mice (“Sp” group), and n = 3 for infected animals from each line at each time point (“Fi4”, “Si4”, “Fi9”, and “Si9” respectively).