Modification: APP: Knock-In
Disease Relevance: Alzheimer's Disease
Strain Name: B6(SJL)-Apptm1.1Aduci/J
Genetic Background: mixed B6J; B6NJ
Availability: Available February, 2019 from The Jackson Laboratory, Stock# 030898
These mice express APP with a “humanized” Aβ sequence. Three point mutations were introduced into exon 14 (exon numbering according to APP695, with 16 exons) of the mouse App gene, to produce three amino acid substitutions within the Aβ sequence (amino acids 5 (G to R), 10 (F to Y) and 13 (R to H) of Aβ). Exon 14 is also flanked by loxP sites. The human Aβ generated by these mice is expected to be more aggregation-prone than the endogenous mouse Aβ. This line may be useful for studying late-onset sporadic Alzheimer’s disease.
Homozygotes are viable and fertile.
A mouse BAC containing the entire App gene was used to amplify and subclone a 3.6-kb region containing App exon 14 (ENSMUSE00000131684). The coding sequence within exon 14 was modified to produce three amino acid substitutions (amino acids 5 (G to R), 10 (F to Y) and 13 (R to H) of Aβ), loxP sites were added flanking exon 14 (this exon starts 17 amino acids N terminally of Aβ and ends at leucine-17 of Aβ), and a neo selection cassette flanked by FRT sites was added. The App gene in C57BL/6N mouse embryonic stem cells (ESC) was modified through homologous recombination using this targeting vector. Mice were generated by injection of the genetically modified ESCs into blastocysts, and chimeric males were bred to FLPe -expressing females to remove the neo cassette, and then the resulting neo-negative males were bred to C57BL/6J females to remove the FLPe transgene. This strain is on a mixed B6J and B6NJ genetic background.
hAbeta-loxP-KI on B6NJ. The hAbeta-loxP-KI allele is also available on a C57BL/6NJ background (strain B6N(Cg)-Apptm1.1Aduci/J, The Jackson Laboratory, Stock# 032013).
hAbeta-loxP-KI on B6J. The hAbeta-loxP-KI allele is also available on a C57BL/6J background (strain B6J(Cg)-Apptm1.1Aduci/J, The Jackson Laboratory, Stock# 031050).
When visualized, these models will distributed over a 18 month timeline demarcated at the following intervals: 1mo, 3mo, 6mo, 9mo, 12mo, 15mo, 18mo+.
- Neuronal Loss
- Synaptic Loss
- Changes in LTP/LTD
- Cognitive Impairment
Changes in LTP/LTD
Last Updated: 09 Apr 2019
No Available Further Reading