# US 7,608,749 B2 · Monitoring APP cleavage in transgenic rodents comprising an APP Swedish mutation > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 7,608,749 B2 - Document ID: US7608749B2 - Status: Granted - Kind: B2 - Application number: 11/643,717 - Filed: 2006-12-20 - Published: 2007-08-23 - Granted: 2009-10-27 - Earliest claimed: 1993-10-27 - Assignees: Elan Pharmaceuticals, Inc.; Eli Lilly and Company - Inventors: Lisa C. McConlogue; Jun Zhao; Sukanto Sinha - Web page: https://patentgrep.com/patent/US7608749B2 ## CPC - C12N 15/8509: {for producing genetically modified animals, e.g. transgenic} - A01K 67/0275: Genetically modified vertebrates, e.g. transgenic - A01K 67/0278: Knock-in vertebrates, e.g. humanised vertebrates - C07K 14/4711: {Alzheimer's disease; Amyloid plaque core protein} - C07K 16/18: against material from animals or humans - A01K 2207/15: Humanized animals - A01K 2217/00: Genetically modified animals - A01K 2217/05: Animals comprising random inserted nucleic acids (transgenic) - A01K 2217/075: inducing loss of function, i.e. knock out - A01K 2227/105: Murine - A01K 2267/0312: Animal model for Alzheimer's disease - A01K 2267/0318: Animal model for neurodegenerative disease, e.g. non- Alzheimer's - A01K 2267/0356: Animal model for processes and diseases of the central nervous system, e.g. stress, learning, schizophrenia, pain, epilepsy - A01K 2267/0393: Animal model comprising a reporter system for screening tests - C12N 2830/008: cell type or tissue specific enhancer/promoter combination - G01N 2800/2821: Alzheimer - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - A01K: ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) ## 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. ## Claims ### Claim 1 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. ### Claim 2 (depends on 1) The method of claim 1, wherein the animal is murine. ### Claim 3 (depends on 1) The method of claim 1, wherein the transgene is nonhomologously integrated. ### Claim 4 (depends on 1) The method of claim 1, wherein the promoter is a neural-specific enolase promoter. ### Claim 5 (depends on 1) The method of claim 1, wherein the rodent is a mouse. ### Claim 6 (depends on 1) The method of claim 1, wherein the agent inhibits a beta-secretase activity associated with the processing. ### Claim 7 (depends on 1) The method of claim 1, wherein the dosage of the agent is from 10 μg/kg to 1 mg/kg. ### Claim 8 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. ### Claim 9 (depends on 8) The method of claim 8, wherein the rodent is murine. ### Claim 10 (depends on 8) The method of claim 8, wherein the rodent is a mouse. ### Claim 11 (depends on 8) The method of claim 8, wherein the transgene is nonhomologously integrated. ### Claim 12 (depends on 8) The method of claim 8, wherein the promoter is a neural specific enolase promoter. ### Claim 13 (depends on 8) The method of claim 8, wherein the agent inhibits a beta-secretase activity associated with the processing. ### Claim 14 (depends on 8) The method of claim 8, wherein the dosage of the agent is from 10 μg/kg to 1 mg/kg.