AD-M2 Mice

Catalog Number: C001541

Genetic Background: C57BL/6JCya

Reproduction: Carrier × WT

Strain Description

The amyloid beta precursor protein (APP) gene encodes a transmembrane precursor protein that acts as a cell surface receptor. This protein is cleaved by secretase to form a polypeptide, part of which forms the protein basis for beta-amyloid plaques (Aβ) found in the brains of Alzheimer’s disease (AD) patients. Mutations in the APP gene are associated with autosomal dominant Alzheimer’s disease and cerebral amyloid angiopathy (CAA) ^[1].

The presenilin 1 (PS1) gene encodes presenilin, which regulates the processing of APP through its action on γ-secretase, a protease responsible for cleaving the APP precursor. Presenilin is also involved in the cleavage of Notch receptors. Mutations in the PS1 or APP genes are found in patients with hereditary Alzheimer’s disease (AD). These disease-associated mutations typically result in an increase in the longer form of β-amyloid protein, the main component of amyloid deposits found in the brains of AD patients ^[2].

This strain rapidly reproduces the main features of AD amyloid pathology and exhibits behavioral defects at different stages, presenting AD-like and progressive cerebral amyloid angiopathy (CAA)-like phenotypes. It is a useful model for studying Aβ42-induced neurodegeneration and amyloid plaque formation within neurons.

Strain Application

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

Validation Data

1. Brain Region β-Amyloid (Aβ) Pathology (10~20 weeks of age)

Figure 1. Immunohistochemical detection of β-amyloid (Aβ) expression in the brains of Wild Type (WT) and AD-M2 mice. The results show that pathological phenotypes of Aβ protein precipitation can be found in the hippocampus and cortex of AD-M2 mice as early as 10 weeks of age, and the pathological Aβ protein precipitation phenotype continues to intensify with age. Both male and female AD-M2 mice were detected with increasing Aβ plaques at 14 and 20 weeks. Compared with AD-M1, AD-M2 mice have earlier onset of Aβ plaques (AD-M2 as late as 10 weeks of age; AD-M1 no earlier than 13 weeks of age); Aβ plaques in AD-M1 are widely present in the hippocampus and cortex, while AD-M2 Aβ plaques are more pronounced in the subiculum of the hippocampus than other brain regions.

2. Brain Region β-Amyloid (Aβ) Pathology (12 months of age)

Figure 2. Immunofluorescence detection of β-amyloid (Aβ) expression in the brains of Wild Type (WT) and AD-M2 mice. The results show that 12-month-old AD-M2 mice have significant β-amyloid (Aβ) deposition (indicated by green fluorescence) in the hippocampus, cortex, thalamus, and spinal cord, while no deposition is found in wild-type mice.

3. Behavioral Testing (6 months of age)

Figure 3. Morris Water Maze test for Wild Type (WT) and AD-M2 mice (6 months of age). In the Place Navigation experiment, both male and female AD-M2 mice took longer to find the escape platform in the water maze than their wild-type littermates, and both began to show significant differences compared to wild-type on the third day of training, with this difference further increasing in subsequent training for female mice. In the Spatial Probe Test, male AD-M2 mice crossed the original platform area significantly fewer times than their wild-type male littermates.

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.