The present invention provides an immuno-deficient animal useful as an animal model for a human disease associated with a first mutation of a target gene, wherein the animal comprises (a) a first human xenograft comprising the target gene comprising the first mutation (b) a second human xenograft comprising the target gene but lacking the first mutation, wherein the first human xenograft and second human xenograft are isogenic. Also provided here are methods of producing the animal model and methods of using such animal model.
