Triple transgenic mouse model of Alzheimer's disease

A triple transgenic mouse-whose genome comprises:

• a knock-in first transgene encoding mutant human presenilin-1 polypeptide having a mutation associated with Alzheimer's disease (AD) or AD-type pathology;
• a second transgene, encoding mutant human Tau protein having a mutation associated with AD or AD-type pathology operably linked to a promoter;
• and
• a third transgene, encoding human β-amyloid precursor protein (βAPP) having a mutation associated with AD or AD-type pathology operably linked to a promoter,
• wherein expression of the transgenes results in a Aβ pathology in the triple transgenic mouse.

A method for making a multi-transgenic mouse the method comprising:

• providing a knock-in mouse whose genome comprises a knock-in first transgene that encodes a mutant human presenilin-1;
• cross-breeding said transgenic mouse with a second knock-in mouse transgenic for said first transgene to obtain an embryo homozygous for said first transgene;
• microinjecting a second transgene into said homozygous embryo, wherein the second transgene is selected from the group consisting of a transgene encoding mutant Tau or a transgenic encoding mutant APP each mutant associated with Alzheimer's disease (AD) or AD-type pathology and each transgene is operably linked to a promoter;
• and
• allowing the embryo to develop to term to produce a multi-transgenic mouse whose genome comprises the two transgenes.

A method for making a triple transgenic mouse, the method comprising:

• providing a mouse whose genome comprises a knock-in first transgene encoding a mutant presenilin-1;
• cross-breeding said transgenic mouse with a second mouse whose genome also comprises said first transgene to obtain an embryo homozygous for said first transgene;
• co-microinjecting a second transgene and a third transgene into said homozygous embryo, wherein said second and third transgenes encode either a mutant Tau or a mutant APP associated with Alzheimer's disease (AD) or AD-type pathology, and wherein each transgene is operably linked to a promoter;
• and allowing the embryo to develop to term to produce a triple transgenic mouse whose genome comprises the three transgenes.

A multi-transgenic mouse produced by the steps of:

• providing a knock-in mouse whose genome comprises a knock-in first transgene that encodes mutant human presenilin-1;
• cross-breeding said transgenic mouse with a second knock-in mouse transgenic for said first transgene to obtain an embryo homozygous for said first transgene;
• microinjecting a second transgene into said homozygous embryo, wherein the second transgene is selected from the group consisting of a transgene encoding mutant Tau or a transgenic encoding mutant APP each mutant associated with Alzheimer's disease (AD) or AD-type pathology and each transgene is operably linked to a promoter;
• and
• allowing the embryo to develop to term to produce a multi-transgenic mouse whose genome comprises the two transgenes.

A triple transgenic mouse, produced by the steps of:

• providing a mouse whose genome comprises a knock-in first transgene encoding a mutant presenilin-1;
• cross-breeding said transgenic mouse with a second mouse whose genome also comprises said first transgene to obtain an embryo homozygous for said first transgene;
• co-microinjecting a second transgene and a third transgene into said homozygous embryo, wherein said second and third transgenes encode either a mutant Tau or a mutant APP associated with Alzheimer's disease (AD) or AD-type pathology, and wherein the transgenes are operably linked to a promoter;
• and
• allowing the embryo to develop to term to produce a triple transgenic mouse whose genome comprises the three transgenes,
• wherein expression of the transgenes results in the deposition of Aβ in the brain of the mouse.

A triple transgenic mouse whose genome comprises:

• a knock-in first transgene encoding a mutant human presenilin-1 polypeptide having a mutation associated with Alzheimer's disease (AD) or AD-type pathology;
• a second transgene, encoding mutant human Tau protein having a mutation associated with AD or AD-type pathology operably linked to a promoter;
• and
• a third transgene, encoding human β-amyloid precursor protein (βAPP) having a mutation associated with AD or AD-type pathology operably linked to a promoter,
• wherein expression of the transgenes results in a Tau pathology and an Aβ pathology in the triple transgenic mouse.

A triple transgenic mouse whose genome comprises:

• a knock-in first transgene encoding a mutant human presenilin-1 polypeptide having a mutation associated with Alzheimer's disease (AD) or AD-type pathology;
• a second transgene, encoding mutant human Tau protein having a mutation associated with AD or AD-type pathology operably linked to a promoter;
• and
• a third transgene, encoding human β-amyloid precursor protein (βAPP) having a mutation associated with AD or AD-type pathology operably linked to a promoter,
• wherein expression of the transgenes results in an AD or AD-type pathology in the triple transgenic mouse.