SHIP deficiency causes Crohn's disease-like ileitis

Kerr, William G; Park, Mi-Young; Maubert, Monique; Engelman, Robert W

Genetic analysis of mice and genome wide association studies have led to the identification of mutations that can predispose to CD with varying probability of incidence and timing of onset. Our analysis suggests that in the laboratory mouse, SHIP is a strong genetic determinant of CD-like pathology, suggesting that a similar situation may also be revealed by close examination of SHIP expression and function in CD patients. Tantalising evidence for a role of SHIP1 in human IBD is suggested by the recent demonstration that a chromosome 2 polymorphism located at 2q37 is associated with a significantly increased and early onset of IBD. 53 The SHIP1 locus is also found in the 2q37 region of human chromosome 2. This potential association merits comparison of SHIP enzymatic activity in IBD patients and normal controls using a recently developed fluorogenic assay that measures SHIP1 activity. 49 Future investigations of cellular and molecular mechanisms responsible for ileitis in SHIP-deficient mice may also provide insights into how immunological alterations contribute to IBD.