hAPP-NL-F Mouse
Product Name
hAPP-NL-F Mouse
Product ID
C002124
Strain Name
C57BL/6Cya-Appem4(hAPP*K670N*M671L*I716F)/Cya
Background
C57BL/6Cya
Status
Citations
0
When using this mouse strain in a publication, please cite “hAPP-NL-F Mouse (Catalog C002124) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Standard products are sold as live mice derived from cryorecovery or expansion. Frozen materials are available upon request. Pricing and lead times depend on real-time inventory.
Gene Name
APP
Gene Alias
AAA, AD1, PN2, ABPP, APPI, CVAP, ABETA, PN-II, preA4, CTFgamma, alpha-sAPP
NCBI ID
Chromosome
Chr 21 (Human)
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.I716F (Iberian) mutation (ATC to TTC), located near the γ-secretase cleavage site, shifts the cleavage precision to increase the ratio of the highly aggregate-prone Aβ42 isoform over Aβ40, thereby facilitating early-onset amyloid plaque deposition [5].
The hAPP-NL-F mouse is an Alzheimer's disease research model generated by replacing the region from downstream of the mouse App signal peptide-coding sequence through part of intron 1 with the "Mutant Human APP CDS-3'UTR of Human APP-WPRE-BGH pA" cassette, while retaining the mouse App signal peptide-coding sequence. In addition, the following point mutations were introduced into the mutant human APP CDS: p.K670N/p.M671L (AAGATG→AATCTG) and p.I716F (ATC→TTC). This model can be used for research on Alzheimer's disease and other neurodegenerative diseases, as well as for the 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.
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 region from downstream of the mouse App signal peptide-coding sequence through part of intron 1 was replaced with the "Mutant Human APP CDS-3'UTR of Human APP-WPRE-BGH pA" cassette, while the mouse App signal peptide-coding sequence was retained. In addition, the following point mutations were introduced into the mutant human APP CDS: p.K670N/p.M671L (AAGATG→AATCTG) and p.I716F (ATC→TTC).
Figure 1. Diagram of the gene editing strategy for the generation of hAPP-NL-F 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.
Contact Us
Connect with our experts for your custom animal model needs. Please fill out the form below to start a conversation or request a quote.
Cyagen values your privacy. We’d like to keep you informed about our latest offerings and insights. Your preferences:
You may unsubscribe from these communications at any time. See our Privacy Policy for details on opting out and data protection.
By clicking the button below, you consent to allow Cyagen to store and process the personal information submitted in this form to provide you the content requested.