Later, two other NOD2 transgenic mice were engineered: one with an insertion causing a frameshift mutation in the final LRR domain, corresponding to one of the most frequent mutation observed in familial Crohn’s disease patients (Maeda et al., 2005), and another with a loss-of-function insertion in the Card15 locus (Kobayashi et al., 2005). This evidence concerns the gene NOD2 and Crohn disease.