| First Author | Watamura N | Year | 2022 |
| Journal | Sci Adv | Volume | 8 |
| Issue | 23 | Pages | eabm6155 |
| PubMed ID | 35675411 | Mgi Jnum | J:326123 |
| Mgi Id | MGI:7293788 | Doi | 10.1126/sciadv.abm6155 |
| Citation | Watamura N, et al. (2022) An isogenic panel of App knock-in mouse models: Profiling beta-secretase inhibition and endosomal abnormalities. Sci Adv 8(23):eabm6155 |
| abstractText | We previously developed single App knock-in mouse models of Alzheimer's disease (AD) that harbor the Swedish and Beyreuther/Iberian mutations with or without the Arctic mutation (App(NL-G-F) and App(NL-F) mice). We have now generated App knock-in mice devoid of the Swedish mutations (App(G-F) mice) and evaluated its characteristics. Amyloid beta peptide (Abeta) pathology was exhibited by App(G-F) mice from 6 to 8 months of age and was accompanied by neuroinflammation. Abeta-secretase inhibitor, verubecestat, attenuated Abeta production in App(G-F) mice, but not in App(NL-G-F) mice, indicating that the App(G-F) mice are more suitable for preclinical studies of beta-secretase inhibition given that most patients with AD do not carry the Swedish mutations. Comparison of isogenic App knock-in lines revealed that multiple factors, including elevated C-terminal fragment beta (CTF-beta) and humanization of Abeta might influence endosomal alterations in vivo. Thus, experimental comparisons between different isogenic App, knock-in mouse lines will provide previously unidentified insights into our understanding of the etiology of AD. |
