This "humanized" App knock-in strain in which 3 point mutations were introduced into exon 14 of the mouse App gene produces a mutant protein that is expected to more readily aggregate. Exon 14 is also flanked by loxP sites. This strain may be useful for studying late-onset sporadic Alzheimer’s disease.
hAbeta-loxP-KI mice are also available on a C57BL/6NJ congenic background (Stock No. 032013).
Frank LaFerla, University of California, Irvine
These hAbeta-loxP-KI knock-in mice, express a mutant "humanized" App allele in which mutations were introduced into exon 14. Exon 14 is flanked by loxP sites. These mice express mouse APP protein with a “humanized” amyloid beta peptide sequence. Homozygotes are viable and fertile. As the mice are characterized, we will modify the strain description and add phenotype data.
Important note about App isoforms and exon numbering: The App-201 isoform (695 aa protein) is encoded by 16 exons, of which the Abeta sequence is encoded by exon 14. The App-206 isoform (770 aa protein) is encoded by 18 exons, of which the Abeta sequence is encoded by exon 16.
The mouse BAC RP23-424A20, containing the entire App gene, was used to amplify and subclone a 3.6kb KpnI – PacI region containing App exon 14 (ENSMUSE00000131684). The Abeta coding sequence within exon 14 was modified by changing three bases to produce three amino acid substitutions (amino acids 5 (G->R), 10 (F->Y) and 13 (R->H)) in exon 14, and loxP sites were added to flank exon 14 and a FRT site flanked neo selection cassette (pM-30) was used to enable G418-selection in mouse ES cells. The targeting vector was electroporated into C57BL/6N derived JM8.N4 ES cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric male animals were bred to Actin-FLPe transgenic female mice, N5 on C57BL/6NTac, (see for example, Stock No. 005703), to remove the neo selection cassette. Male offspring mice that no longer carried the selection cassette were then bred to C57BL/6J females to remove the Tg(ACTFLPe)9205Dym transgene. The mice were then intercrossed to produce homozygotes that were subsequently intercrossed for 7 to 8 generations to generate homozygotes. The mice were then bred to C57BL/6NTac wild-type mice once. Heterozygotes were intercrossed to generate homozygotes for the hAbeta-loxP-KI (APPKI-hAbwt) allele that are also homozygous for wild-type Nnt.
Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6NJ oocytes (Stock No. 005304). This strain is on a mixed B6J and B6N genetic background.
|Allele Name||targeted mutation 1.1, Frank LaFerla|
|Allele Type||Targeted (Conditional ready (e.g. floxed), Humanized sequence)|
|Allele Synonym(s)||Apptm1.1Aduci; targeted mutation 1.1, Frank LaFerla|
|Gene Symbol and Name||App, amyloid beta (A4) precursor protein|
|Gene Synonym(s)||Cvap; E030013M08Rik; betaAPP; Alzheimer disease amyloid beta protein; E030013M08Rik; Adap; ABETA; APPI; ABPP; AD1; AL024401; CTFgamma; PN-II; PN2; cerebrovascular amyloid peptide; CVAP; appican; Adap; protease nexin II; AAA; expressed sequence AL024401; RIKEN cDNA E030013M08 gene; Abeta; Cvap; preA4|
|Strain of Origin||C57BL/6N|
|Molecular Note||The targeting construct includes a loxP site upstream of exon 14, 3 point mutations inserted into exon 14 to create amino acid substitutions (amino acids 5 (G->R), 10 (F->Y) and 13 (R->H)) (ENSMUSE00000131684), a loxP site downstream of exon 14 and a FRT-flanked neo selection cassette, which is removed by FLP-mediated recombination.|
When maintaining a live colony, these mice can be bred as homozygotes.
When using the hAbeta-loxP-KI on mixed B6J and B6NJ mouse strain in a publication, please cite the originating article(s) and include JAX stock #030898 in your Materials and Methods section.
|Heterozygous for App<tm1.1Lfa>|
We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.
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