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US 7,608,749 B2Granted
Monitoring APP cleavage in transgenic rodents comprising an APP Swedish mutation
AssigneesElan Pharmaceuticals, Inc., Eli Lilly and Company
InventorsLisa C. McConlogue, Jun Zhao, Sukanto Sinha
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Abstract
The invention provides transgenic non-human animals and transgenic non-human mammalian cells harboring a transgene encoding an APP polypeptide comprising the Swedish mutation.
Claims14
A method of screening for an agent that affects processing of amyloid precursor protein, the method comprising:
- providing a transgenic rodent comprising a diploid genome comprising a transgene comprising in operable linkage a promoter and a DNA segment encoding a human APP polypeptide comprising the Swedish mutation wherein the amino acid residues at positions corresponding to positions 595 and 596 in human APP695 are asparagine and leucine, respectively, wherein the transgene is expressed to produce a human APP polypeptide having the Swedish mutation, and wherein the polypeptide is processed to ATF-βAPP in a sufficient amount to be detectable in a brain homogenate of said transgenic rodent;
- contacting the transgenic rodent with the agent;
- monitoring processing of the amyloid precursor protein polypeptide in a brain homogenate of the contacted transgenic rodent compared to the processing in a control transgenic rodent to indicate the agent affects the processing.
A method of preparing a composition, comprising an agent that affects processing of amyloid precursor protein, the method comprising:
- providing a transgenic rodent comprising a diploid genome comprising a transgene comprising in operable linkage a promoter and a DNA segment encoding a human APP polypeptide comprising the Swedish mutation wherein the amino acid residues at positions corresponding to positions 595 and 596 in human APP695 are asparagine and leucine, respectively, wherein the transgene is expressed to produce a human APP polypeptide having the Swedish mutation, and wherein the polypeptide is processed to ATF-βAPP in a sufficient amount to be detectable in a brain homogenate of said transgenic rodent;
- contacting the transgenic rodent with the agent;
- monitoring processing of the amyloid precursor protein polypeptide in a brain homogenate of the contacted transgenic rodent compared to the processing in a control transgenic rodent to indicate the agent affects the processing;
- and
- incorporating the agent into a composition with a pharmaceutical carrier.
2 more elements
Dependencies are inferred from the claim text.