Question:

Genome Wide Association Studies (GWAS) identified the gene encoding Leucine-Rich Repeat Kinase 2 (LRRK2) as high susceptibility gene for Inflammatory Bowel Disease (IBD). We aimed to show the role of LRRK2 in chronic Dextran Sodium Sulfate (DSS) colitis in mice that is closest to human IBD.

Methods:

Chronic DSS colitis was induced in LRRK2 ^-/- mice (KO) and wildtype mice (WT) (n=10 each) before experimental and control (n=10 KO; n=10 WT) animals were sacrificed for sample collection. Colitis severity was evaluated by monitoring of weight, colon length, spleen weight, myeloperoxidase (MPO) activity, colonoscopy score, and histological score. Expression of IL-6, IL-10, IL-18, TNFα, INFγ, iNOS, and MCP1 was determined in RNA isolated from colonic tissue and mesenterial lymph nodes by real-timePCR.

Results:

None of the assessed parameters revealed any difference between LRKK2 ^-/- and WT mice. However, colon length, spleen weight, MPO activity, MEICS and histoscore showed significant differences between control and experimental groups indicating successful induction of the chronic DSS colitis.

Conclusions:

Our data show that a deficiency in LRRK2 is not accompanied by significantly higher susceptibility or disease severity in mice suffering from chronic DSS induced colitis which stands in contrast to results regarding an acute DSS induced colitis model. This leads to the hypothesis, that LRRK2 deficiency may play a major role in acute colitis which is mainly perpetuated by a hyperactive innate immune response in contrast to chronic colitis that is in turn perpetuated mostly by an overshooting adaptive immune response.