Genes: APP, RAGE (AGER)
Mutations: APP KM670/671NL (Swedish), APP V717F (Indiana)
Modification: APP: Transgenic; RAGE (AGER): Transgenic
Disease Relevance: Alzheimer's Disease
Strain Name: N/A
Genetic Background: C57BL/6
Availability: Available through Shirley ShiDu Yan
Bigenic mice expressing dominant-negative RAGE as well as mutant APP displayed diminished neuropathology compared with mice expressing mutant APP alone, including the area occupied by acetylcholinesterase-positive fibers in the subiculum at three to four and 14 to 18 months of age (Arancio et al., 2004).
No abnormalities were reported with respect to reproductive fitness, development, basic neurological functioning, or longevity (Arancio et al., 2004).
Mice expressing a dominant-negative form of RAGE comprising a truncated form of the receptor with intact extracellular and membrane-spanning portions, but a deleted cytosolic tail driven by the PDGF-β promoter were crossed with mice expressing human APP carrying the Swedish and Indiana mutations driven by PDGF-β promoter (The Jackson Lab: Stock# 004661--now extinct).
Research Models Citations
- Arancio O, Zhang HP, Chen X, Lin C, Trinchese F, Puzzo D, Liu S, Hegde A, Yan SF, Stern A, Luddy JS, Lue LF, Walker DG, Roher A, Buttini M, Mucke L, Li W, Schmidt AM, Kindy M, Hyslop PA, Stern DM, Du Yan SS. RAGE potentiates Abeta-induced perturbation of neuronal function in transgenic mice. EMBO J. 2004 Oct 13;23(20):4096-105. PubMed.