Double transgenic mice overexressing human beta secretase and human APP-London
AssigneeHoffmann-La Roche Inc.
InventorsHelmut Jacobsen, Laurence Mosbach-Ozmen, Peter Nelboeck-Hochstetter
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Abstract
The present invention relates to a novel animal model for amyloidopathies, especially Alzheimer' disease overexpressing human BACE and human APP London. This novel animal model exhibits several aspects of amyloidopathy. The present invention also relates to a method for producing the double transgenic animals, to cells and cell lines derived from these animals and to a kit comprising these cells. Moreover, a method for the evaluation of the in vivo effects of beta-secretase activity on A-beta peptide generation, amyloidosis, neurodegeneration and AD pathology in these animals is provided.
Claims9
A method of producing a double transgenic mouse whose genome incorporates DNA comprising a coding sequence encoding SEQ ID NO. 9 operably linked to a prion regulatory promoter sequence and a coding sequence which encodes SEQ ID NO. 1 operably linked to a Thy-1 regulatory promoter sequence, which method comprises:
- (a) introducing a DNA construct comprising a coding sequence which encodes SEQ ID NO. 9 and a prion regulatory sequence operably linked to the coding sequence into a mouse cell or embryo and generating a transgenic mouse from said cell or embryo;
- (b) introducing a DNA construct comprising a coding sequence which encodes SEQ ID NO. 1 and a Thy-1 regulatory sequence operably linked to the coding sequence into a mouse cell or embryo and generating a transgenic mouse from said cell or embryo;
- and
- (c) crossbreeding the transgenic mice generated in steps (a) and (b);
- wherein the double transgenic mouse exhibits increased pathology as demonstrated by increased deposition of A-beta peptide relative to an APP London single transgenic mouse.
A method of producing a double transgenic mouse whose genome incorporates DNA comprising a coding sequence encoding SEQ ID NO. 9 operably linked to a prion regulatory promoter sequence and a coding sequence which encodes SEQ ID NO. 1 operably linked to a Thy-1 regulatory promoter sequence, which method comprises:
- (a) co-injecting into a mouse cell or embryo:
- (1) a DNA construct comprising a coding sequence encoding SEQ ID NO. 9 operably linked to a prion regulatory promoter sequence;
- and (2) a DNA construct comprising a coding sequence which encodes SEQ ID NO. 1 operably linked to a Thy-1 regulatory promoter sequence;
- and
- (b) generating a double transgenic mouse from said cell or embryo;
- wherein the double transgenic mouse exhibits increased pathology as demonstrated by increased deposition of A-beta peptide relative to an APP London single transgenic mouse.
A double transgenic mouse whose genome incorporates DNA comprising:
- (1) a coding sequence which encodes SEQ ID NO. 1 operably linked to a Thy-1 regulatory sequence and (2) a coding sequence encoding SEQ ID NO. 9 operably linked to a prion regulatory sequence;
- wherein the double transgenic mouse exhibits increased pathology as demonstrated by increased deposition of A-beta peptide relative to an APP London single transgenic mouse.
Dependencies are inferred from the claim text.