Transgenic mice displaying the amyloid-forming pathology of alzheimer's disease

• US 5,387,742 A
• Filed: 06/17/1991
• Issued: 02/07/1995
• Est. Priority Date: 06/15/1990
• Status: Expired due to Term

• Current Assignee: Scios, Inc. (Johnson & Johnson)
• Original Assignee: Scios, Inc. (Johnson & Johnson)
• Inventors: Cordell, Barbara
• Primary Examiner(s): Weimar, Elizabeth C.
• Assistant Examiner(s): Crouch, Deborah
• Application Number:
  US07/716,725
• Time in Patent Office: 1,331 Days
• Field of Search: 800/2, 435/6, 514/44
• US Class Current: 800/12
• CPC Class Codes: A01K 2207/15 Humanized animals
• CPC Class Codes: A01K 2217/00 Genetically modified animals
• CPC Class Codes: A01K 2217/05 Animals comprising random inserted nucleic acids (transgenic)
• CPC Class Codes: A01K 2227/105 Murine
• CPC Class Codes: A01K 2267/0312 Animal model for Alzheimer's disease
• 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: C12N 15/85 for animal cells
• CPC Class Codes: C12N 15/8509 for producing genetically modified animals, e.g. transgenic
• CPC Class Codes: C12N 2830/002 inducible enhancer/promoter combination, e.g. hypoxia, iron, transcription factor
• CPC Class Codes: C12N 2830/008 cell type or tissue specific enhancer/promoter combination
• CPC Class Codes: C12N 2830/15 chimeric enhancer/promoter combination
• CPC Class Codes: C12N 2830/42 being an intron or intervening sequence for splicing and/or stability of RNA
• CPC Class Codes: C12N 2830/85 mammalian

Abstract

Cloned recombinant or synthetic DNA sequences related to the pathology of Alzheimer'"'"'s disease are injected into fertilized mouse eggs. The injected eggs are implanted in pseudo pregnant females and are grown to term to provide transgenic mice whose cells express proteins related to the pathology of Alzheimer'"'"'s disease. The injected sequences are constructed having promoter sequences connected so as to express the desired protein in brain tissues of the transgenic mouse. The proteins which are preferably ubiquitously expressed include (1) β-amyloid core precursor proteins; and (2) β-amyloid related precursor proteins; and (3) serine protease inhibitor. The transgenic mice provide useful models for studying compounds being tested for their usefulness in treating Alzheimer'"'"'s disease, and for studying the in vivo interrelationships of these proteins to each other.

Claims

1. A transgenic mouse whose cells contain a DNA sequence, comprising:

nerve tissue specific promoter; and

a DNA sequence which encodes a β

-amyloid precursor protein selected from the group consisting of A751 and A770,

wherein the promoter and DNA sequence which encodes the precursor protein are operatively linked to each other and integrated in the genome of the mouse and expressed to form β

-amyloid protein deposits in the brain of the mouse.

2. The transgenic mouse of claim 1, wherein the promoter is a neuronal specific enolase promoter.

3. The transgenic mouse of claim 1, wherein the promoter is rat neuronal specific enolase promoter.

4. A transgenic mouse whose cells contain a DNA sequence, comprising:

a nerve tissue specific promoter, wherein the promoter is rat neuronal specific enolase promoter; and

a DNA sequence which encodes β

-amyloid precursor protein A751,

wherein the promoter and DNA sequence which encodes the precursor protein are operatively linked to each other and integrated in the genome of the mouse and expressed to form β

-amyloid protein deposits in the brain of the mouse.