Transgenic mouse having a disrupted amyloid precursor protein gene
AssigneesMerck & Co., Inc., Merck Frosst Canada, Inc.
InventorsHui Zheng, Howard Y. Chen, Myrna E. Trumbauer, Leonardus H. T. van der Ploeg, Guy Seabrook, Dalip Sirinathsinghji
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Abstract
The present invention relates to a transgenic nonhuman animal lacking native amyloid precursor protein. The transgenic mouse of the invention may be used in the study of Alzheimer's Disease and disorders involving the central nervous system.
Claims12
A transgenic mouse whose genome comprises a disruption of the gene encoding amyloid precursor protein (APP), wherein functional APP is not produced and the mouse exhibits a phenotype selected from impaired long-term potentiation, a decrease in presynaptic markers, a decrease in dendritic marker MAP-2 in the cortex, an increase of dendritic marker MAP-2 in CA1 pyramidal cells in the hippocampus or weight loss as compared to a wild-type mice.
A method of producing a mouse whose genome comprises a disruption of the gene encoding amyloid precursor protein (APP), the method comprising:
- (a) providing a gene encoding mouse APP, wherein the gene comprise a disruption such that function APP is not expressed from said gene;
- (b) introducing the disrupted gene into mouse embryonic stem cells;
- (c) selecting those embryonic stem cells that comprise the disrupted gene encoding APP;
- (d) introducing an embryonic stem cells of step (c) into a mouse blastocyst;
- (e) transferring the blastocyst of step (d) to pseudopregnant mouse, and
- (f) allowing the transferred blastocyst to develop into a mouse chimeric for the disruption.
Dependencies are inferred from the claim text.