Abstract: The present invention provides for genetically engineered non-human animals, including but not limited to mice, which lack one or more endogenous neurofilament gene. Human neurofilament genes may be introduced into such genetically non-human animals (referred to hereafter as “knockout animals”) to produce improved models of the physiology of human neurofilament proteins which may be used to study human neurofilament-associated neurodegenerative conditions.