| First Author | Jankowsky JL | Year | 2007 |
| Journal | J Biol Chem | Volume | 282 |
| Issue | 31 | Pages | 22707-20 |
| PubMed ID | 17556372 | Mgi Jnum | J:124804 |
| Mgi Id | MGI:3722556 | Doi | 10.1074/jbc.M611050200 |
| Citation | Jankowsky JL, et al. (2007) Rodent A beta modulates the solubility and distribution of amyloid deposits in transgenic mice. J Biol Chem 282(31):22707-20 |
| abstractText | The amino acid sequence of amyloid precursor protein (APP) is highly conserved, and age-related A beta aggregates have been described in a variety of vertebrate animals, with the notable exception of mice and rats. Three amino acid substitutions distinguish mouse and human A beta that might contribute to their differing properties in vivo. To examine the amyloidogenic potential of mouse A beta, we studied several lines of transgenic mice overexpressing wild-type mouse amyloid precursor protein (moAPP) either alone or in conjunction with mutant PS1 (PS1dE9). Neither overexpression of moAPP alone nor co-expression with PS1dE9 caused mice to develop Alzheimer-type amyloid pathology by 24 months of age. We further tested whether mouse A beta could accelerate the deposition of human A beta by crossing the moAPP transgenic mice to a bigenic line expressing human APPswe with PS1dE9. The triple transgenic animals (moAPP x APPswe/PS1dE9) produced 20% more A beta but formed amyloid deposits no faster and to no greater extent than APPswe/PS1dE9 siblings. Instead, the additional mouse A beta increased the detergent solubility of accumulated amyloid and exacerbated amyloid deposition in the vasculature. These findings suggest that, although mouse A beta does not influence the rate of amyloid formation, the incorporation of A beta peptides with differing sequences alters the solubility and localization of the resulting aggregates. |
