PRNP and amyotrophic lateral sclerosis: TDP-43 is a major component of ubiquitinated cytoplasmic inclusions found ubiquitously in amyotrophic lateral sclerosis patients.53 Mutations in TDP-43 are also associated with development of amyotrophic lateral sclerosis.54 The TDP-43A315T mouse overexpresses human TDP-43 harbouring the disease-linked A315T amino acid substitution mutation. Expression is driven off the murine prion protein (PrP) promoter.55