CRISPR/Cas9-generated rodent models of congenital hydrocephalus resulting from mutations in different hydrocephalus-related genes, such as L1cam and Ccdc39, can be interbred to investigate epistatic interactions previously believed to affect mutation penetrance and ventricular size in other models of hydrocephalus (Weller and Gärtner, 2001; Zhang et al., 2006). The gene discussed is L1CAM; the disease is congenital hydrocephalus.