Alagille syndrome is a genetic disorder characterized by severe liver and heart abnormalities, and ocular, vertebral and craniofacial malformations. Most cases of this disease are associated with mutations in a gene encoding a Notch ligand called JAG1, but how signalling was affected through different Notch receptors was poorly understood and previous disease models did not recapitulate all its features. To produce the new mouse model, researchers generated mice homozygous for a missense mutation (H268Q) in JAG1 (Jag1Ndr/Ndr) in which bile duct development is disrupted and most features of Alagille syndrome are reproduced. Using this model, the investigators studied Notch signalling and showed that the JAG1Ndrmutation generates a hypomorphic ligand that binds to NOTCH2 but not NOTCH1.