Transgenic mice over-expressing receptor for advanced glycation endproduct (RAGE) and mutant APP in brain and uses thereof

US6563015B1 · kind B1 · utility

Assignee

• The Trustees of Columbia University in the City of New York · US

Inventors

• David M. Stern · Great Neck, US
• Ann Marie Schmidt · Franklin Lakes, US
• Shi Du Yan · New York, US

Key dates

• Filing date: Aug 14, 2000
• Grant date: May 13, 2003
• Expiry date: Aug 14, 2020

Classification

• Technology area (CPC G): Physics
• CPC primary: G01N2800/52
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The invention provides for a non-human transgenic animal whose cells contain a recombinant DNA sequence comprising: (a) a nerve tissue specific promoter operatively linked to a DNA sequence which encodes human receptor for advanced glycation endproducts (RAGE), and (b) a nerve tissue specific promoter operatively linked to a DNA sequence encoding a mutant human amyloid precursor protein hAPP695, hAPP751 and hAPP770 bearing mutations linked to familial Alzheimer's disease in humans, wherein said non-human transgenic animal exhibits at least one phenotype from the group consisting of: increased expression of M-CSF gene in cerebral cortex; increased expression of IL-6 gene in cerebral cortex; increased neuronal stress; increased neurotoxicity; neuron loss; increased level of activated form of caspase 3 in brain; and increased level of phosphorylated tau protein in brain.