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.
The hAbeta-loxP-KI allele is available on a C57BL/6J congenic background (Stock No. 031050), on a C57BL/6NJ congenic background (Stock No. 032013) and on a mixed C57BL/6J and C57BL/6NJ background (Stock No. 030898).
Frank LaFerla, University of California, Irvine
Genetic Background | Generation |
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?+pN1F7
|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Conditional ready (e.g. floxed), Humanized sequence) | App | amyloid beta (A4) precursor protein |
Starting at:
$255.00 Domestic price for female 4-week |
510.00 Domestic price for breeder pair |
$2,854.50 Domestic price Cryo Recovery |
hAbeta-loxP-KI knock-in is a mutant "humanized" App allele in which three mutations were introduced into the mouse App exon that encodes the Aβ fragment (see below), such that the sequence now encodes the same amino acids as human. This exon is also flanked by loxP sites. These hAbeta-loxP-KI 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 hAbeta-loxP-KI allele is available on a C57BL/6J congenic background (Stock No. 031050), on a C57BL/6NJ congenic background (Stock No. 032013) and on a mixed C57BL/6J and C57BL/6NJ background (Stock No. 030898).
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 (Aβ-encoding amino acids 5 (G->R), 10 (F->Y) and 13 (R->H)). 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 |
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Allele Type | Targeted (Conditional ready (e.g. floxed), Humanized sequence) |
Allele Synonym(s) | APPKI-hAbeta |
Gene Symbol and Name | App, amyloid beta (A4) precursor protein |
Gene Synonym(s) | |
Strain of Origin | C57BL/6N |
Chromosome | 16 |
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.
Service/Product | Description | Price |
---|---|---|
Heterozygous for App<tm1.1Lfa> |
Frozen Mouse Embryo | B6(SJL)-App<tm1.1Aduci>/J | $2595.00 |
Frozen Mouse Embryo | B6(SJL)-App<tm1.1Aduci>/J | $2595.00 |
Frozen Mouse Embryo | B6(SJL)-App<tm1.1Aduci>/J | $3373.50 |
Frozen Mouse Embryo | B6(SJL)-App<tm1.1Aduci>/J | $3373.50 |
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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