JAM-C−/− mice in the C57BL/6 genetic background developed a severe and progressive hydrocephalus, characterized by extremely enlarged lateral ventricles accompanied by hippocampal dislocation, cortical thinning, loss of proper cortical layering with subsequent reactive gliosis as well as hemorrhages in different brain compartments and obstruction of CSF circulation. Here, JAM3 is linked to Hydrocephalus.