One of the insights in IBD physiology reviewed by Bouma and Strober 1 is that the host genetic background determines susceptibility to colitis. Various studies have described that the differences in susceptibility to chemically induced colitis is strain dependent.
The C3H/HeJ, C3H/HeJBir 30 and C57BL/6 strains are highly susceptible to DSS-induced acute colitis, while BALB/c mice only develop colitis when higher percentages of DSS are administered.31 Also, the recovery phase of the disease after 5 days of administering DSS differs between C57BL/6 and BALB/c mice—C57BL/6 mice develop a severe chronic inflammation, whereas BALB/c mice resolve the colitis after the acute phase.31
In TNBS colitis the difference in susceptibility to colitis between SJL/J (susceptible) and C57BL/6 (resistant) mice is associated with the ability to mount an IL-12 response to lipopolysaccharide (LPS).32,33 IL-12 is the major cytokine for the differentiation of Th1-CD4+ T cells. For the mouse models in which T cells play a role it is important to realize that, in general, mice with a C57BL/6 background are more prone to develop a Th1 response, whereas BALB/c mice have a tendency to develop a Th2 response 34 when exposed to pathogens.
In the T-cell transfer model mice both C57BL/6 13 and BALB/c 35 backgrounds are used. In IL-10 knockout mice severe intestinal lesions develop in mice with a 129SvEv or BALB/c background, while C57BL/6 strains are relatively resistant to the development of colitis.36,37 In C57BL/6 mice colitis induction can be accelerated by peroral administration of piroxicam, a nonselective nonsteroidal anti-inflammatory drug (NSAID).38
To avoid the differences in susceptibility introduced by these extreme phenotypes, it might be an option to introduce the use of a collaborative cross-mouse genetic reference population as a new less biased resource in IBD research.39,40
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