B6(SJL)-Apoe^{tm1.1(APOE*4)Adiuj} Plcg2^em3Adiuj App^em1Adiuj Trem2^em1Adiuj/J

Stock number: 034454
Product name: Plcg2*M28L/hAbeta/APOE4/Trem2*R47H
Research areas: Cardiovascular Research, Metabolism Research, Neurobiology Research, Research Tools

Description

Plcg2*M28L/hAbeta/APOE4/Trem2*R47H mice express a CRISPR/Cas9-generated mutant of the phospholipase C, gamma 2 gene carrying the M28L missense mutation associated with increased risk of Alzheimer's disease.
This mutation is maintained with the hAbeta/APOE4/Trem2*R47H mutations (Stock No. 030670) intended to increase risk of late-onset Alzheimer's disease: a humanized Apoe knock-in mutation (sequence coding for human isoform E4), 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) and a CRISPR/Cas9-generated R47H point mutation of the Trem2 gene.

Detailed description

This quadruple mutant strain incorporates a humanized Apoe knock-in mutation (sequence coding for isoform E4), a CRISPR/Cas9 generated mutant of the Plcg2 gene with the M28L mutation, CRISPR/cas9-generated G601R, F606Y, and R609H mutations of the App gene, and a CRISPR/Cas9-generated R47H point mutation of the Trem2 gene. These mice may be suitable for use in studies related to Alzheimer's disease, lipoproteins, arteriosclerosis, and coronary heart disease.

The viability/fertility of Plcg2^em3Adiuj homozygotes has not been assessed (February, 2020).

Development

The following mutations were intercrossed:

Apoe^{tm1.1(APOE*4)Adiuj} - see Stock No. 027894

Plcg2^em3Adiuj - see Stock No. 030674

App^em1Adiuj - see Stock No. 030670

Trem2^em1Adiuj - see Stock No. 027918

Allele

Symbol: Trem2^em1Adiuj
Name: endonuclease-mediated mutation 1, MODEL-AD Center
MGI accession ID: MGI:5770794
Generation method: Endonuclease-mediated
Attributes: Humanized sequence
Marker symbol: Trem2
Marker name: triggering receptor expressed on myeloid cells 2
Chromosome: 17
Strain of origin: C57BL/6J
Molecular note: The allele was generated by injecting cas9 nuclease and a single guide RNA designed to introduce a R47H point mutation with two silent mutations (lysine AAG>AAA and alanine GCC>GCA) into the gene.

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^{tm1.1(APOE*4)Adiuj}
Name: targeted mutation 1.1, MODEL-AD Center
MGI accession ID: MGI:5810209
Generation method: Targeted
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Apoe
Marker name: apolipoprotein E
Chromosome: 7
Strain of origin: C57BL/6J
Expressed genes: APOE,apolipoprotein E,human
Site of expression: Endogenous mouse elements direct human APOE gene sequence (including exons 2, 3 and 4 and some 3' UTR sequence).
Molecular note: The targeting vector contains a 3' FRT flanked neo cassette and 1.5 kb of human APOE gene sequence including exons 2, 3, 4 and a portion of the 3'UTR sequence (the APOE4 isoform) which is used to replace exons 2, 3 and most of exon 4 of the endogenous sequence. The human ApoE sequence carries a 2 nucleotide A to T substitution in intron 3. Flp-mediated recombination removed the FRT-flanked neo cassette.

Allele

Symbol: Plcg2^em3Adiuj
Name: endonuclease-mediated mutation 3, MODEL-AD Center
MGI accession ID: MGI:6164497
Generation method: Endonuclease-mediated
Attributes: Humanized sequence
Marker symbol: Plcg2
Marker name: phospholipase C, gamma 2
Chromosome: 8
Strain of origin: B6(SJL)-Apoe^{tm1.1(APOE*4)Adiuj} Trem2^em1Adiuj/J
Molecular note: The allele was generated by injecting cas9 nuclease and a single guide RNA designed to introduce a M28L point mutation.