USP18 and Hydrocephalus: It has been demonstrated that homozygous Usp18 knockout mice with additional breeding within a C56/B6 and 129 mixed background show a nearly normal lifespan, while homozygous Usp18 knockout mice in an initial C57/B6 and 129 mixed strain show a decreased lifespan due to neurological abnormalities related to brain ependymal cell death resulting in aqueduct stenosis and hydrocephalus [47].