Transgenic mice expressing human p25
US6693226B1 · kind B1 · utility
Assignee
Inventors
Key dates
| Filing date | Feb 2, 2000 |
| Grant date | Feb 17, 2004 |
| Priority date | — |
| Expiry date | Feb 2, 2020 |
Classification
- Technology area (CPC C)Chemistry; Metallurgy
- CPC primaryC12N2830/008
- WIPO fieldBiotechnology
- WIPO sectorChemistry
Abstract
The invention provides transgenic, non-human animals and transgenic non-human mammalian cells harboring a transgene encoding a p25 (activator of the protein kinase cdk 5) polypeptide. The two neuropathological lesions associated with Alzheimer's disease (AD) are amyloid plaques and neurofibrillary tangles (NFTs), composed predominantly of amyloid &bgr; peptides and hyperphosphorylated tau, respectvely. While animal models for plaque formation exist, there is no animal model that recapitulates the formation of NFTs. This invention provides transgenic mice that overexpress human p25, an activator of cdk5, resulting in tau that is hyperphosphorylated at AD-relevant epitopes. Deposition of tau is detected in the amygdala, thalamus and cortex. Increased phosphorylated neurofilament, silver-positive neurons and neuronal death are also observed in these regions. We conclude that the overexpression of p25, an activator of cdk5, is sufficient to produce hyperphosphorylation of tau and neuronal death. The p25 transgenic mouse represents the first model for tau pathology in AD.
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.