APP770 mutant in alzheimer's disease

• US 5,877,015 A
• Filed: 01/21/1992
• Issued: 03/02/1999
• Est. Priority Date: 01/21/1991
• Status: Expired due to Term

• Current Assignee: Elan Pharmaceuticals Incorporated (Perrigo Company PLC)
• Original Assignee: Imperial College of Science Technology & Medicine (Imperial College London)
• Inventors: Goate, Alison Mary, Owen, Michael John, Mullan, Michael John, Chartier-Harlin, Marie-Christine, Hardy, John Anthony
• Primary Examiner(s): Wax, Robert A.
• Assistant Examiner(s): Lau, Kawai
• Application Number:
  US08/104,165
• Time in Patent Office: 2,597 Days
• Field of Search: 435/29, 435/240.1, 435/252.3, 435/6, 435/325, 536/23.5
• US Class Current: 435/325
• 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 2217/072 maintaining or altering function, i.e. knock in
• 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: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: C07K 14/4711 Alzheimer's disease; Amyloid plaque core protein
• CPC Class Codes: C07K 14/575 Hormones derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin C07K14/665, e.g. corticotropin C07K14/695
• 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: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: C12Q 2600/172 Haplotypes

Abstract

Model systems of Alzheimer'"'"'s disease comprise a DNA sequence encoding an amyloid precursor protein (APP) isoform or fragment that has an amino acid substitution. The substituted amino acid may be other than valine at the amino acid position corresponding to amino acid residue position 717 of APP770. Methods of determining genetic predisposition to Alzheimer'"'"'s disease are also disclosed.

Claims

1. An isolated polynucleotide comprising a nucleic acid sequence encoding a codon 717 mutant of human amyloid precursor protein 770 (APP770), or an isoform or fragment of APP770 having a mutant amino acid residue at the position encoded by codon 717.

2. An isolated polynucleotide of claim 1, wherein the amino acid at the position encoded by codon 717 is an isoleucine, glycine, or phenylalanine.

3. An isolated polynucleotide of claim 1, wherein the nucleic acid sequence is a cDNA.

4. A transgenic cell comprising a nucleic acid segment encoding a codon position 717 mutant of human amyloid precursor protein 770 (APP770), or an APP770 isoform or fragment of APP770 having the mutation.

5. A transgenic cell of claim 4, which is a primary or immortalized eukaryotic cell line.

6. A transgenic cell of claim 4, which is a bacterium.

7. A transgenic cell of claim 4, wherein the segment is integrated into the cell'"'"'s genome.

8. A cultured human primary or immortalized cell, comprising a nucleic acid segment encoding a codon position 717 mutant of human amyloid precursor protein 770 (APP770), or an APP770 isoform or fragment of APP770 having the mutation.

9. The cultured human primary or immortalized cell of claim 8, wherein the cell is an immortalized cell.

10. A polynucleotide comprising a nucleic acid segment encoding a codon 717 mutant of human amyloid precursor protein 770 (APP770), or an isoform or fragment of APP770 having a mutant amino acid residue at the position encoded by codon 717, wherein the nucleic acid segment is in operable linkage with a promoter not naturally associated with the human amyloid precursor protein.

11. The polynucleotide of claims 10, wherein the nucleic acid segment incorporates at least one substitution other than at codon 717 relative to a nucleic acid sequence encoding a natural human amyloid precursor protein.

12. A nonhuman cell containing a nucleic acid sequence encoding a codon 717 mutant of human amyloid precursor protein 770 (APP770), or an isoform or fragment of APP770 having a mutant amino acid residue at the position encoded by codon 717.