B-Psen1*M146L*E120K mice_Biocytogen Pharmaceuticals (Beijing) Co., Ltd._Biocytogen, drug development, antibody discovery

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B-Psen1*M146L*E120K mice

Strain Name	C57BL/6JNifdc-Psen1^tm1Bcgen /Bcgen	Common Name	B-Psen1M146LE120K mice
Background	C57BL/6JNifdc	Catalog number	112977
Aliases	AD3, FAD, PS1, PS-1, S182, CMD1U, PSNL1, ACNINV3
NCBI Gene ID	5663

Description

Mutations in the PSEN1 gene, encoding presenilin-1 (PS1), are the most common cause of familial Alzheimer’s disease (FAD).
Alzheimer’s disease (AD) is characterized by the extracellular buildup of β-amyloid (Aβ) plaques and the intracellular aggregation of neurofibrillary tangles (NFTs), which are composed of hyperphosphorylated tau.
APP is sequentially proteolytically cleaved by β- and γ-secretase, neurotoxic Aβ peptides are released, which can accumulate into oligomer aggregate. PSEN1 genes encode the major component of y-secretase, which is responsible for sequential proteolytic cleavages of amyloid precursor proteins and the subsequent formation of amyloid-β peptides. Mutations in the PSEN1 increase the production of Aβ peptide.
In addition to amyloid precursor protein (APP) cleavage, PSEN1 can also affect other processes, such as Notch signaling, β-cadherin processing, and calcium metabolism.
Gene editing strategy: The 120 and 146 amino acids Glu and Met of mouse PSEN1 was mutated as Lys and Leu in B-Psen1*M146L*E120K mice.
mRNA expression analysis: Mouse Psen1 mRNA was detectable in wild-type C57BL/6JNifdc mice and homozygous B-Psen1*M146L*E120K mice. Sequence assays showed the homozygous B-Psen1*M146L*E120K mice consists of G to A point mutation at amino acid 120 and A to C point mutation at amino acid 146.
Application: This product is used for pharmacodynamics and safety evaluation of Alzheimer’s disease (AD).

Targeting strategy

Gene targeting strategy for B-Psen1*P117L mice. The 120 and 146 amino acids Glu and Met of mouse Psen1 was mutated as Lys and Leu in B-Psen1*M146L*E120K mice.

mRNA expression analysis

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Psen1 mRNA expression in wild-type C57BL/6J mice and homozygous B-Psen1*M146L*E120K mice by RT-PCR. Brain RNA were isolated from wild-type C57BL/6J mice (+/+) and homozygous B-Psen1*M146L*E120K mice (Mut/Mut), then cDNA libraries were synthesized by reverse transcription, followed by PCR with mouse Psen1 primers. Mouse Psen1 mRNA was detectable in wild-type C57BL/6J and homozygous mice. And the point mutations were confirmed via Sanger Sequencing.

Protein expression analysis

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Western blot analysis of PSEN1 protein expression in homozygous B-Psen1*M146L*E120K mice. Cortex and hippocampus lysates were collected from wild-type C57BL/6J mice (+/+) and homozygous B-Psen1*M146L*E120K mice (Mut/Mut), and then analyzed by western blot with anti-PSEN1 antibody (CST, #5643). 40 μg total proteins were loaded for western blotting analysis. PSEN1 was detected in cortex and hippocampus both in wild-type and homozygous B-Psen1*M146L*E120K mice.