AD-M1 Mice

Catalog Number: C001210

Genetic Background: C57BL/6JCya

Strain Description

The Amyloid beta precursor protein (APP) gene encodes cell surface receptors and transmembrane precursor proteins, the latter of which are cleaved by secretase to form polypeptides, some of which form the protein basis of beta-amyloid plaques (Aβ) in the brain of patients with Alzheimer's disease (AD), and mutations in this gene have been associated with autosomal dominant Alzheimer's disease and cerebral arterial amyloidosis ^[1].

The progerin protein 1 (PS1) gene encodes progerin that regulates APP processing through its action on γ-secretase, a protease responsible for cleaving APP precursors, and in addition, progerin is involved in Notch receptor cleavage. Patients with hereditary Alzheimer's disease carry mutations in the progerin protein or amyloid precursor protein, and these disease-related mutations usually lead to an increase in the longer form of β-amyloid, the main component of amyloid deposits found in the brains of AD patients ^[2].

Allele Type

Transgenic (TG)

Application

• Research on Alzheimer's Disease (AD);
• Research on Cerebral Amyloid Angiopathy (CAA);
• Research on Notch signaling pathway.

Validation Data

1. Survival and growth curves

Figure 1. Survival and Growth Curves of AD-M1 Mice (Female, n=50; Male, n=50; Monitored for 56 Weeks).

2. Amyloid β-protein (Aβ) pathology in the Brain

Figure 2. Age-dependent accumulation of Aβ plaques in the hippocampus and cortex of AD-M1 mice. Aβ plaques were significantly increased in the corresponding regions of AD-M1 mice at 45 weeks of age and 60 weeks of age compared with 27-week-old AD-M1 mice. In addition, Aβ plaques were widespread in both the hippocampus and cortex.

3. Morris Water Maze

1) 6-month-old

Figure 3. Morris Water Maze test for Wild Type (WT) and AD-M1 mice at 6 months of age. In the Place Navigation experiment, male and female AD-M1 mice took longer to find the escape platform in the water maze than their wild-type littermates, but only the male mice showed significant differences on the third day of training. In the Spatial Probe Test, female AD-M1 mice crossed the original platform area significantly fewer times than their wild-type female littermates.

2) 10-month-old

Figure 4. Morris Water Maze performance of 10-month-old AD-M1 mice, with or without Donepezil treatment for 2 months (The significant differences between groups were analyzed by one-way ANOVA method, *P<0.05, **P<0.01, ***P<0.001, ^#P<0.05, ^##P<0.01). The Morris Water Maze test included a learning period followed by a testing session. Mice were trained for 5 days, and on day 6, the number of platform crossings and escape latency were recorded. During the learning phase of the Morris water maze, the WT-saline and AD-M1+Donepezil groups exhibited progressively shorter latencies over the days, indicating intact spatial learning and locomotor activity. In contrast, the AD-M1+Vehicle group did not show a significant reduction in latency over time, suggesting impaired spatial learning. During the testing phase, both the WT-saline and AD-M1+Donepezil groups demonstrated shorter latencies and a higher number of platform crossings compared to the AD-M1+Vehicle group. These findings confirm the spatial learning deficits in AD-M1 mice, and demonstrate that Donepezil effectively mitigates these impairments.

Publications
[1]Meng J, Chen Y, Bi F, Li H, Chang C, Liu W. Pterostilbene attenuates amyloid-β induced neurotoxicity with regulating PDE4A-CREB-BDNF pathway. Am J Transl Res. 2019 Oct 15;11(10):6356-6369.
[2]Li R, Xiong W, Li B, Li Y, Fang B, Wang X, Ren F. Plasmalogen Improves Memory Function by Regulating Neurogenesis in a Mouse Model of Alzheimer's Diseases. Int J Mol Sci. 2023 Jul 31;24(15):12234.
[3]Zhou R, Wang L, Chen L, Feng X, Zhou R, Xiang P, Wen J, Huang Y, Zhou H. Bone Marrow-Derived GCA+ Immune Cells Drive Alzheimer's Disease Progression. Adv Sci (Weinh). 2023 Dec;10(36):e2303402.

References
[1]Hefter D, Ludewig S, Draguhn A, Korte M. Amyloid, APP, and Electrical Activity of the Brain. Neuroscientist. 2020 Jun;26(3):231-251.
[2]Bagaria J, Bagyinszky E, An SSA. Genetics, Functions, and Clinical Impact of Presenilin-1 (PSEN1) Gene. Int J Mol Sci. 2022 Sep 19;23(18):10970.