Quadruple transgenic non-human animal

A method for generating a transgenic non-human animal whose genome comprises transgenic DNA encoding a human APP Swedish or APP London, a human Presenilin 2 protein comprising N1411, substitution and a heavy and a light chain of a human antibody directed against the beta amyloid peptide comprising

• a) co-injecting a genetic construct comprising a first transgenic DNA sequence encoding a human APP Swedish or APP London, and a genetic construct comprising a second transgenic DNA sequence encoding a human Presenilin 2 protein with a N1411 substitution into a non-human zygote or an non-human embryonic stem cell, and generating a double transgenic non-human animal from said zygote or embryonic stem cell;
• b) co-injecting a genetic construct comprising a third transgenic DNA sequence encoding a light chain of a human antibody directed against the amyloid peptide, and a genetic construct comprising a fourth transgenic DNA sequence encoding a heavy chain of said human antibody into a non-human zygote or a non-human embryonic stem cell and generating a double transgenic non-human animal from said zygote or embryonic stem cell, and
• c) mating transgenic animals of a) and b) and thereby producing a quadruple transgenic non-human animal whose genome comprises transgenic DNA encoding, a human APP Swedish or APP London, a human Presenilin 2 protein comprising a N1411 substitution, and a heavy and a light chain of a human antibody directed against the beta amyloid peptide.

A method for generating a transgenic non-human animal expressing a human APP Swedish or APP London, a human Presenilin 2 protein comprising N1411 substitution, and a heavy and a light chain of a human antibody directed against human beta amyloid peptide comprising

• a) co-injecting a genetic construct comprising a first transgenic DNA sequence encoding a human APP Swedish or APP London wherein said first transgenic DNA sequence is operably linked to a first promoter, and a genetic construct comprising a second transgenic DNA sequence encoding a human Presenilin 2 protein with a N1411 substitution into a non-human zygote or an non-human embryonic stem cell, wherein said second transgenic DNA sequence is operably linked to a second promoter, and generating a double transgenic non-human animal from said zygote or embryonic stem cell;
• b) co-injecting a genetic construct comprising a third transgenic DNA sequence encoding a light chain of a human antibody directed against the human amyloid peptide, wherein said third transgenic DNA sequence is operably linked to a third promoter and a genetic construct comprising a fourth transgenic DNA sequence encoding a heavy chain of said human antibody into a non-human zygote or a non-human embryonic stem cell, wherein said fourth transgenic DNA sequences is operably linked to a fourth promoter, and generating a double transgenic non-human animal from said zygote or embryonic stem cell, and
• c) mating transgenic animals of a) and b) and thereby producing a quadruple transgenic non-human animal expressing a human APP Swedish or APP London, a human Presenilin 2 protein comprising a N1411 substitution, and a heavy and a light chain of a human antibody directed against the beta amyloid peptide.