hAbeta/APOE3 mice carry an R130C mutation in the Apoetm1.1(APOE*4)Adiuj allele (Stock No. 027894) that expresses the human APOE isoform E3 (APOE3 KI), and a CRISPR/Cas9-generated App allele with a humanized Abeta1-42 region (G601R, F606Y, R609H in the mouse gene, corresponding to amino acid positions 676, 681, 684 in the human APP locus). These mice may be suitable for use in studies related to Alzheimer's disease, lipoproteins, arteriosclerosis, and coronary heart disease.
Mike Sasner, The Jackson Laboratory
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Endonuclease-mediated (Inserted expressed sequence, Humanized sequence) | Apoe | apolipoprotein E |
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Endonuclease-mediated (Humanized sequence) | App | amyloid beta (A4) precursor protein |
hAbeta/APOE3 mice carry an R130C mutation in the Apoetm1.1(APOE*4)Adiuj allele (Stock No. 027894) that expresses the human APOE isoform E3 (APOE3 KI), and a CRISPR/Cas9-generated App allele with a humanized Abeta1-42 region (G601R, F606Y, R609H in the mouse gene, corresponding to amino acid positions 676, 681, 684 in the human APP locus). These mice may be suitable for use in studies related to Alzheimer's disease, lipoproteins, arteriosclerosis, and coronary heart disease.
Apoeem2(APOE*)Adiuj - see Stock No. 029018
To generate this APOE3 KI, a mutagenic oligo based approach was used. Plasmids encoding a signal guide RNA designed to introduce a R130C point mutation into the Apoetm1.1(APOE*4)Adiuj allele (Stock No. 027894) and the cas9 nuclease were introduced into the cytoplasm-derived fertilized eggs with well recognized pronuclei. Resultant mice were identified by sequencing and PCR and further bred to C57BL/6J (Stock No. 000664) to develop the colony.
Appem1Adiuj - see Stock No. 030670
Plasmids encoding a single guide RNA designed to introduce the G601R, F606Y, and R609H point mutations into the App gene and the cas9 nuclease were introduced into the cytoplasm of Stock No. 028709-derived fertilized eggs with well recognized pronuclei. G601R corresponds to a GGA to CGA nucleotide change, F606Y represents a TTT to TAT nucleotide mutation, and R609H incorporates a CGC to CAT nucleotide change. The Apoetm1.1(APOE*4)Adiuj and Trem2em1Adiuj mutations were bred away.
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.
Expressed Gene | APOE, apolipoprotein E, human |
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Site of Expression | |
Site of Expression |
Allele Name | endonuclease-mediated mutation 1, MODEL-AD Center |
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Allele Type | Endonuclease-mediated (Inserted expressed sequence, Humanized sequence) |
Allele Synonym(s) | APOEepsilon3 |
Gene Symbol and Name | Apoe, apolipoprotein E |
Gene Synonym(s) | |
Expressed Gene | APOE, apolipoprotein E, human |
Strain of Origin | B6(SJL)-Apoetm1.1(APOE*4)Adiuj/J |
Chromosome | 7 |
Molecular Note | CRISPR-Cas9 methodology introduced a R130C point mutation into the human APOE protein carried by the Apoetm1.1(APOE*4)Adpmc allele. |
Allele Name | endonuclease-mediated mutation 1, MODEL-AD Center |
---|---|
Allele Type | Endonuclease-mediated (Humanized sequence) |
Allele Synonym(s) | |
Gene Symbol and Name | App, amyloid beta (A4) precursor protein |
Gene Synonym(s) | |
Strain of Origin | B6(SJL)-Apoetm1.1(APOE*4)Adiuj Trem2em1Adiuj/J |
Chromosome | 16 |
Molecular Note | CRISPR/Cas9 genome editing methodologies are used to introduce G601R, F606Y, and R609H point mutations into the App gene. G601R corresponds to a GGA to CGA nucleotide change, F606Y represents a TTT to TAT change, and R609H incorporates a CGC to CAT nucleotide change. |
Compound heterozygotes and homozygotes are viable and fertile.
When using the hAbeta/APOE3 mouse strain in a publication, please cite the originating article(s) and include JAX stock #034455 in your Materials and Methods section.
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