This model may serve generally useful for understanding how mutations in SKI homologs elicit trichohepatoenteric syndrome in humans (Fabre et al., 2012), loss of pelota/dom34 yields embryonic lethality in mice (Adham et al., 2003), loss of a nonstop protein decay factor (lister) yields neurodegenerative phenotypes in mice (Chu et al., 2009), and dysregulation of nonsense decay contributes to tumorigenicity in humans and mice models (Wang et al., 2011; Popp and Maquat, 2015). The gene discussed is SKI; the disease is trichohepatoenteric syndrome.