B6(SJL)-Apoe^{em2(APOE*)Adiuj} App^em1Adiuj/J

Stock number: 034455
Product name: hAbeta/APOE3
Research areas: Cardiovascular Research, Metabolism Research, Neurobiology Research, Research Tools

Description

hAbeta/APOE3 mice carry an R130C mutation in the Apoe^{tm1.1(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.

Detailed description

hAbeta/APOE3 mice carry an R130C mutation in the Apoe^{tm1.1(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.

Development

Apoe^{em2(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 Apoe^{tm1.1(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.

App^em1Adiuj - 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 Apoe^{tm1.1(APOE*4)Adiuj} and Trem2^em1Adiuj 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.

Allele

Symbol: App^em1Adiuj
Name: endonuclease-mediated mutation 1, MODEL-AD Center
MGI accession ID: MGI:6164022
Generation method: Endonuclease-mediated
Attributes: Humanized sequence
Marker symbol: App
Marker name: amyloid beta (A4) precursor protein
Chromosome: 16
Strain of origin: B6(SJL)-Apoe^{tm1.1(APOE*4)Adiuj} Trem2^em1Adiuj/J
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.

Allele

Symbol: Apoe^{em2(APOE*)Adiuj}
Name: endonuclease-mediated mutation 1, MODEL-AD Center
MGI accession ID: MGI:5907023
Generation method: Endonuclease-mediated
Attributes: Inserted expressed sequence; Humanized sequence
Synonyms: APOE^epsilon3
Marker symbol: Apoe
Marker name: apolipoprotein E
Chromosome: 7
Strain of origin: B6(SJL)-Apoe^{tm1.1(APOE*4)Adiuj}/J
Expressed genes: APOE,apolipoprotein E,human
Molecular note: CRISPR-Cas9 methodology introduced a R130C point mutation into the human APOE protein carried by the Apoe^{tm1.1(APOE*4)Adpmc} allele.