Transgenic animals harboring APP allele having swedish mutation

• US 5,612,486 A
• Filed: 11/01/1993
• Issued: 03/18/1997
• Est. Priority Date: 10/27/1993
• Status: Expired due to Term

• Current Assignee: Eli Lilly and Company, Elan Pharmaceuticals Incorporated (Perrigo Company PLC)
• Original Assignee: Eli Lilly and Company, Athena Neurosciences Incorporated (Perrigo Company PLC)
• Inventors: Zhao, Jun, McConlogue, Lisa C.
• Primary Examiner(s): Ziska, Suzanne E.
• Application Number:
  US08/148,211
• Time in Patent Office: 1,233 Days
• Field of Search: 800/2, 536/23.5
• US Class Current: 800/12
• CPC Class Codes: A01K 2217/05 Animals comprising random inserted nucleic acids (transgenic)
• CPC Class Codes: A01K 2217/075 inducing loss of function, i.e. knock out
• CPC Class Codes: A01K 2227/105 Murine
• CPC Class Codes: A01K 2267/0312 Animal model for Alzheimer's disease
• CPC Class Codes: A01K 2267/0318 Animal model for neurodegenerative disease, e.g. non- Alzheimer's
• CPC Class Codes: A01K 67/0278 Knock-in vertebrates, e.g. humanised vertebrates
• CPC Class Codes: C07K 14/4711 Alzheimer's disease; Amyloid plaque core protein
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C12N 15/8509 for producing genetically modified animals, e.g. transgenic
• CPC Class Codes: C12N 2830/008 cell type or tissue specific enhancer/promoter combination
• CPC Class Codes: G01N 2333/4709 Amyloid plaque core protein
• CPC Class Codes: G01N 2500/02 Screening involving studying the effect of compounds C on the interaction between interacting molecules A and B (e.g. A = enzyme and B = substrate for A, or A = receptor and B = ligand for the receptor)
• CPC Class Codes: G01N 2800/2821 Alzheimer
• CPC Class Codes: G01N 33/5008 for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
• CPC Class Codes: G01N 33/502 for testing non-proliferative effects
• CPC Class Codes: G01N 33/5058 Neurological cells
• CPC Class Codes: G01N 33/5091 for testing the pathological state of an organism
• CPC Class Codes: G01N 33/6896 Neurological disorders, e.g. Alzheimer's disease

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

1. A transgenic rodent comprising a diploid genome comprising a transgene encoding a heterologous APP polypeptide having 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 said polypeptide is processed to ATF-betaAPP in a sufficient amount to be detectable in a brain homogenate of said transgenic rodent.

2. A transgenic rodent of claim 1, wherein the animal is murine.

3. A transgenic rodent of claim 2, wherein the transgene is nonhomologously integrated.

4. A transgenic rodent of claim 1, wherein the heterologous APP polypeptide having the Swedish mutation is expressed under the transcriptional control of a neural-specific enolase promoter.