B6.Cg-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax, more commonly referred to as APP/PS1, is a strain of mouse model based on the popular C57BL/6J strain. It carries mutations that make it useful in the study of Alzheimer’s disease.
APP/PS1 mice are descended from the C57BL/6J strain (B6), which was developed by Little in 1921. A stock of B6 mice was later deliberately engineered to create a suitable model for Alzheimer’s disease (AD) research.
The requisite transgenes were inserted at one locus in the pronuclei of B6C3HF2 mice, which were then backcrossed for eight generations with normal C57BL/6J to produce the current APP/PS1 strain.
APP/PS1 mice have black fur and are generally very similar in appearance to the closely related C57BL/6J strain.
Behavioral Characteristics & Handling
As an AD model, APP/PS1 mice display marked deficits in learning and memory when compared to wild-type mice. Researchers report impaired recognition memory in the novel object recognition test, as well as impaired reference memory in the radial arm maze.
Activity in the open field test did not differ between APP/PS1 and control C57BL/6J mice, suggesting the inserted transgenes do not affect exploratory behavior. Results from the elevated plus maze test of anxiety are inconclusive.
No data could be found on the handling of this strain. Researchers should thus exercise caution and may want to opt for a different strain if a guarantee of high docility is a necessity.
The APP/PS1 strain has been genetically engineered to express proteins which induce a disease phenotype resembling AD in humans.
The mice were modified with two plasmids, containing the transgenes Mo/HuAPP695swe and PS1-dE9, designed to be controlled by prion promoter elements. The first of these genes express a mouse amyloid beta 4 protein altered to more closely resemble the human analog, and the second expresses a human mutant presenilin 1 protein.
Histological evidence shows that APP/PS1 mice develop deposits of amyloid beta protein in the brain by around six months of age. The accumulation of amyloid plaques is much more pronounced in females than in males and is seen more in the molecular layer of the cerebellum than in the granular layer.
Hemizygous APP/PS1 mice can show frequent seizures, as seen via EEG recordings; approximately a quarter of these transgenic mice will experience a seizure by three months of age, and over half by five months. Mortality reaches nearly 40% by 18 weeks of age.
Seizures are not seen with the related B6C3-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax strain, developed on a C57BL/6;C3H background rather than pure C57BL/6J.
Major Experimental Uses
The APP/PS1 strain was deliberately designed to serve as a model for the study of AD, and so is still mainly applied to that line of research. It is especially useful for the study of familial AD engendered by presinilin, APP or PSEN1 mutations. Also, their exhibition of seizures means these mice can also be used in epilepsy research.
The deficits in learning and memory that they show as a result of their AD-like phenotype means these mice are not suitable for most normal behavioral experiments.
- B6.Cg-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax. 2018. B6.Cg-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax. [ONLINE] Available at: https://www.jax.org/strain/005864. [Accessed 14 November 2018].
- MGI – Inbred Strains: C57BL. 2018. MGI – Inbred Strains: C57BL. [ONLINE] Available at: http://www.informatics.jax.org/inbred_strains/mouse/docs/C57BL.shtml. [Accessed 12 November 2018].
- Webster SJ, Bachstetter AD, Van Eldik LJ. Comprehensive behavioral characterization of an APP/PS-1 double knock-in mouse model of Alzheimer’s disease. Alzheimers Res Ther. 2013. 5(3):28.
- Kenghoe Loka, Hong Zhaoa, Hanlin Shena, Zejian Wanga, Xiang Gaob, Wenjuan Zhaoa, Ming Yina. Characterization of the APP/PS1 mouse model of Alzheimer’s disease in senescence accelerated background. Neuroscience Letters. 557. 2013. 84–89.