Patent ID: 7081561

Claim:
A gene-targeted mouse whose genome comprises a modified endogenous apolipoprotein E (apoE) allele, wherein said modified allele comprises an apoE-encoding nucleic acid under transcriptional control of endogenous ApoE regulatory sequences, wherein the modified allele encodes a modified apoE polypeptide that exhibits domain interaction characteristic of human apolipoprotein E4 (apoE4), wherein the modified apoE polypeptide comprises a Thr→Arg substitution at a position equivalent to amino acid 61 of human apoE4, wherein the gene targeted mouse is homozygous for the modified apoE allele, and wherein the modified apoE polypeptide exhibits preferential binding to lower density lipoproteins when compared to unmodified, wild-type mouse apoE, and wherein the mouse exhibits apoE4-related neurodegeneration.