| First Author | Vidal R | Year | 2012 |
| Journal | Prion | Volume | 6 |
| Issue | 4 | Pages | 346-9 |
| PubMed ID | 22874668 | Mgi Jnum | J:197584 |
| Mgi Id | MGI:5493395 | Doi | 10.4161/pri.21023 |
| Citation | Vidal R, et al. (2012) Generation of a novel murine model of Abeta deposition based on the expression of human wild-type amyloid precursor protein gene. Prion 6(4):346-9 |
| abstractText | Mouse models of Alzheimer disease (AD) have been generated based on Amyloid-beta Precursor Protein (AbetaPP) and the Presenilin (PSEN) gene mutations associated with familial AD (FAD). Such models have provided valuable insights into AD pathogenesis and represent an important research tool for the discovery of potential treatments. To model amyloid deposition in AD, we generated a new mouse line based on the presence of two copies of the genomic region encoding human wild-type AbetaPP as well as a mutation (L166P) in the murine Psen1. By ~6 months of age, these mice have begun to develop cerebral Abeta pathology with a significant increase in the levels of AbetaPP C-terminal fragments and Abeta42, as well as increase Abeta42/Abeta40 ratio. Since in the brain and other tissues of these mice, wild-type human AbetaPP mRNA and protein levels are comparable to those of endogenous AbetaPP, this model may allow studies about the role of AbetaPP isoforms in the pathogenesis of AD. This animal model may be suitable to test drugs aimed at inhibiting expression or altering splicing and processing of AbetaPP, without artifacts associated with the presence of mutations in AbetaPP or overexpression due to the use of exogenous promoters. These features of the new model are of critical importance in assessing the success of therapeutic interventions. |
