Mice lacking SH2 domain–containing inositol 5′ phosphatase-1 (SHIP-1) develop spontaneous CD-like ileitis with near 100% penetrance, and exhibit many key CD features including Th1/Th17 skewed transmural inflammation, marked neutrophil infiltration into ileal tissue, the formation of granulomas, and microbial dysbiosis [26–29]. This evidence concerns the gene INPP5D and Cowden disease.