A genetically modified mouse expressing human APOE4p and mouse Trem2 p.R47H and methods of use thereof

摘要

Genetically modified mice characterized by one or more symptoms or signs associated with expression of human APOE4p and mouse Trem2p and relevant to non- familial late-onset Alzheimer's disease are provided wherein the genome of the mouse includes: 1) a DNA sequence encoding a human APOE4 protein (APOE4p) operably linked to a promoter; and 2) a DNA sequence encoding a mouse Trem2 protein having a mutation p,R47H (Trem2p) operably linked to a promoter, such that the mouse expresses human APOE4p and mouse Trem2p. Methods ace provided for screening for a compound for use in the treatment of Alzheimer's disease using such genetically modified mice.