-実験動物開発室-

App knock-in mouse strains: new models for
Alzheimer’s disease

C57BL/6-App<tm1(NL)Tcs>/TcsRbrc (RBRC06342)

C57BL/6-App<tm2(NL-F)Tcs>/TcsRbrc (RBRC06343)

C57BL/6-App<tm3(NL-G-F)Tcs>/TcsRbrc (RBRC06344)

Courtesy of Takaomi C. Saido, Ph.D. and Takashi Saito, Ph.D.

App knock-in mice exhibit AD patient-like Aβ₄₂-dominant plaque deposition concomitantly with neuroinflammation and memory impairment. Importantly, the mice live normally, in contrast to previous APP overexpression-based models which are aggressive and often die of unknown cause(s).

Takaomi C. Saido, Takashi Saito, and colleagues at RIKEN Brain Science Institute generated App knock-in mice with the Swedish mutation (App^NL/NL, RBRC06342); Swedish and Iberian mutations (App^NL-F/NL-F, RBRC06343); and Swedish, Iberian, and Arctic mutations (App^{NL-G-F/NL-G-F}, RBRC06344) [2-4]. The Swedish KM670/671NL mutation increases the total amount of Aβ, while the Beyreuther/Iberian I716F mutation increases the ratio of Aβ₄₂ to Aβ₄₀. App^NL-F/NL-F mice, which carry the Swedish and Iberian mutations, show Aβ deposition in the cortex and hippocampus at 6 months and memory impairment at 18 months, whereas App^NL/NL mice, which carry only the Swedish mutation, are normal. The last group of generated mice, App^{NL-G-F/NL-G-F}, mice carry the Swedish mutation, Iberian mutation, and Arctic E693G mutation, which accelerates Aβ aggregation starting at 2 months and memory impairment at 6 months.

App^NL-F/NL-F and App^{NL-G-F/NL-G-F} mice show typical Aβ pathology, neuroinflammation, and memory impairment, without overexpressing APP or interrupting other mouse genes. These mouse strains will stimulate further research identifying the mechanisms and pathways involved in Aβ amyloidosis. They are listed on the research models database of the web-based scientific community Alzforum [5].