Provided is a genetically modified non-human animal, in which at least one copy of the endogenous nucleotide sequence encoding Protein C in the genome of said the non-human animal has been replaced by a nucleotide sequence encoding human Protein C or a functional fragment or variant thereof. Also provided are vectors, cells, and methods for the production of such non-human animals. Further provided are methods of testing agents for their ability to alter to the level and/or functional activity of human protein C, for example, to test their potential therapeutic efficacy.