BMC Genomics 2006, 7:42 http://www.biomedcentral.com/1471-2164/7/42 Table 3: GO terms significantly associated with the differentially expressed genes No. of RefSeqs associated with term Fisher exact score GO term Response to biotic stimulus Response to stimulus Response to external stimulus Defense response Response to stress Organismal physiological process Immune response Response to pest/pathogen/ parasite Cytoskeleton Cellular Process Susceptible Resistant (indels) while MutSβ repairs longer 2–6 bp indels [41]. A change in expression of either MSH6 or MSH3 can subse- quently lead to a change in the MutSα to MutSβ ratio. The MutSα complex is induced at the transcriptional level in response to radiation [42]. Expression of MSH6 may be higher in the duodenum of susceptible animals in order to assist these animals to cope with toxic and mutagenic insults present in ingested food. GPX2 is another stress response gene more highly expressed in the intestine of the susceptible animals. This gene encodes the selenopro- tein, gastrointestinal glutathione peroxidase 2, which catalyses the reduction of peroxides by reduced glutath- ione and protects the cell against oxidative damage. This gene is known to be induced in response to oxidative stress [43]. The interferon inducible gene IFI35 is induced at the transcriptional level in response to interferons, and complexes with the N-Myc interacting protein, NMI, to form a high molecular weight cytosolic complex [44]. The precise function of this complex, however, remains unknown. UBD encodes a small ubiquitin-like modifier protein also known as FAT10. UBD is induced by the cytokines IFNγ and TNFα [45] and can bind proteins and target them for degradation by the proteasome in a cytokine inducible, irreversible, ubiquitin-independent manner [46]. SERPING1, also known as C1 inhibitor (C1- INH), encodes an IFNγ inducible [47] serine protease inhibitor of the complement and contact systems. This protein therefore exhibits an anti-inflammatory effect [48,49]. SERPING1 is known to help prevent endotoxic shock [50] and is under investigation as a clinical treat- ment for a variety of diseases [51]. TFF3 encodes intestinal trefoil factor 3. Trefoil factors are involved in mucosal pro- tection and healing and are induced during inflammation and in response to gastrointestinal mucosa damage [52]. The increased expression of so many stress response genes in the intestine of the susceptible animals appears to indi- cate that these animals are responding to gut insult and inflammation. Alternatively, these animals may constitu- 6 7 6 5 5 5 4 3 3 9 0.00012 0.00028 0.00067 0.00072 0.00124 0.00425 0.00486 0.00956 0.0397 0.0426 tively express these stress response genes at inappropriate levels in the absence of challenge. Interestingly, stress response genes did not appear to be more highly expressed in the duodenum of susceptible animals after natural challenge with nematodes [25] indicating that these genes may be inappropriately regulated in the gas- trointestinal tract of susceptible animals. The source of stress to the intestinal tract of the susceptible animals remains unknown. Some of the stress response genes more highly expressed in susceptible animals are known to play a role in protecting the cell against oxida- tive damage. MSH6 is involved in repairing DNA lesions caused by oxidation [53] while GPX2 reduces DNA dam- aging agents [54]. HMOX1 is also strongly induced by oxi- dative stress and is involved in heme degradation [55]. Chronic gut inflammation is associated with enhanced production of leukocyte derived oxidants [56]. Therefore the gastrointestinal tract of the susceptible animals may be suffering damage from reactive oxygen species. This could come from a number of sources such as aberrant cellular metabolism or phagocytic leukocytes responding to an infection. Indeed some of the stress proteins more highly expressed in the gastrointestinal tract of the suscep- tible animals are involved in the immune response and are inducible by pro-inflammatory cytokines. Therefore although free from gastrointestinal nematodes, the sus- ceptible animals may be responding to infection by other viral or bacterial pathogens. A number of pro-apoptotic genes are more highly expressed in the intestine of the susceptible animals. These genes promote apoptosis in response to stress. Apoptosis is a primary form of defence against infection, stress, damage or injury in the cell. MSH6, TRAF4, UBD and BMF can all induce a protective apoptotic response in cells [45,57-59]. The soluable form of HLA-A has also been shown to trigger apoptosis of CD8+ T cells [60]. Page 6 of 12 (page number not for citation purposes)