huAPP-Aβ-NL-G-F-I Mouse
Product Name
huAPP-Aβ-NL-G-F-I Mouse
Product ID
C002033
Strain Name
C57BL/6JCya-Appem1(hAPP*K670N*M671L*E693G*I716F*V717I)/Cya
Backgroud
C57BL/6JCya
Status
When using this mouse strain in a publication, please cite “huAPP-Aβ-NL-G-F-I Mouse (Catalog C002033) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Gene Name
Gene Alias
AAA, AD1, PN2, ABPP, APPI, CVAP, ABETA, PN-II, preA4, CTFgamma, alpha-sAPP
NCBI ID
Chromosome
Chr 21
MGI ID
Datasheet
Strain Description
The APP gene encodes the Amyloid Precursor Protein, a type I transmembrane glycoprotein that is ubiquitously expressed but reaches its highest levels in the central nervous system, particularly in the cerebral cortex and hippocampus. Following translation, the APP protein is proteolytically processed via two primary pathways: the non-amyloidogenic pathway, which prevents Aβ formation, and the amyloidogenic pathway, where sequential cleavage by β-secretase (BACE1) and γ-secretase releases amyloid-beta (Aβ) peptides [1]. While its precise physiological role remains an area of active research, APP is known to function in synaptic formation and repair, anterograde neuronal transport, and cell-to-cell adhesion [2]. Pathological mutations or duplications of the APP gene are primary drivers of Alzheimer’s Disease (AD) and Cerebral Amyloid Angiopathy (CAA), characterized by the extracellular accumulation of Aβ plaques and vascular deposits that lead to neurodegeneration and cognitive decline [3].
Pathogenic point mutations in the APP gene typically disrupt these proteolytic pathways, favoring the production or aggregation of neurotoxic peptides. The p.K670N/p.M671L (Swedish) double mutation (AAGATG to AATCTG) occurs at the β-secretase cleavage site, significantly increasing the production of total Aβ by enhancing BACE1 affinity [4]. In contrast, the p.E693G (Arctic) mutation (GAA to GGA) is located within the Aβ sequence itself; it does not increase peptide quantity but dramatically accelerates the formation of protofibrils [5]. Mutations near the γ-secretase cleavage site, such as p.I716F (Iberian) (ATC to TTC) and p.V717I (London) (GTC to ATC), shift the cleavage precision to increase the ratio of the highly aggregate-prone Aβ42 isoform over Aβ40, thereby facilitating early-onset amyloid plaque deposition [6].
The huAPP-Aβ-NL-G-F-I mouse is an Alzheimer's disease research model generated by replacing the sequence from upstream of exon 16 to downstream of exon 17 in the murine App gene with the corresponding sequence from the human APP gene. Simultaneously, the p.K670N/p.M671L (AAGATG to AATCTG), p.I716F (ATC to TTC), p.E693G (GAA to GGA) and p.V717I (GTC to ATC) point mutations were introduced into exon 16 and exon 17 of human APP gene. This model is suitable for studying neurodegenerative diseases such as Alzheimer's disease (AD), as well as for the research, development, and efficacy evaluation of AD therapeutic strategies targeting APP.
Reference
Cole SL, Vassar R. The Alzheimer's disease beta-secretase enzyme, BACE1. Mol Neurodegener. 2007 Nov 15;2:22.
Zheng H, Koo EH. The amyloid precursor protein: beyond amyloid. Mol Neurodegener. 2006 Jul 3;1:5.
Grangeon L, Charbonnier C, Zarea A, Rousseau S, Rovelet-Lecrux A, Bendetowicz D, Lemaitre M, Malrain C, Quillard-Muraine M, Cassinari K, Maltete D, Pariente J, Moreaud O, Magnin E, Cretin B, Mackowiak MA, Sillaire AR, Vercelletto M, Dionet E, Felician O, Rod-Olivieri P, Thomas-Antérion C, Godeneche G, Sauvée M, Cartz-Piver L, Le Ber I, Chauvire V, Jonveaux T, Balageas AC, Laquerriere A, Duyckaerts C, Vital A, de Paula AM, Meyronet D, Guyant-Marechal L, Hannequin D, Tournier-Lasserve E, Campion D; CNR-MAJ collaborators; Nicolas G, Wallon D. Phenotype and imaging features associated with APP duplications. Alzheimers Res Ther. 2023 May 11;15(1):93.
Tcw J, Goate AM. Genetics of β-Amyloid Precursor Protein in Alzheimer's Disease. Cold Spring Harb Perspect Med. 2017 Jun 1;7(6):a024539.
Wang S, Ichinomiya T, Savchenko P, Devulapalli S, Wang D, Beltz G, Saito T, Saido TC, Wagner SL, Patel HH, Head BP. Age-Dependent Behavioral and Metabolic Assessment of AppNL-G-F/NL-G-F Knock-in (KI) Mice. Front Mol Neurosci. 2022 Jul 29;15:909989.
Valle ML. A Novel APP Knock-In Mouse Model to Study the Protective Effects of the Icelandic Mutation In Vivo. J Neurosci. 2025 Apr 23;45(17):e0164252025.
Strain Strategy
The sequences from upstream of exon 16 to downstream of exon 17 of mouse App were replaced with the sequences from upstream of exon 16 to downstream of exon 17 of human APP. And the p.K670N/p.M671L (AAGATG to AATCTG), p.I716F (ATC to TTC), p.E693G (GAA to GGA) and p.V717I (GTC to ATC) point mutations were introduced into exon 16 and exon 17 of human APP gene.
Figure 1. Diagram of the gene editing strategy for the generation of huAPP-Aβ-NL-G-F-I mice.
Application Area
Research on Alzheimer's disease (AD);
Research on Cerebral Amyloid Angiopathy (CAA);
Preclinical research such as the development, screening, and efficacy evaluation of APP-targeted therapeutic drugs.
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