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.
Mike Sasner, The Jackson Laboratory
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Endonuclease-mediated (Humanized sequence) | Trem2 | triggering receptor expressed on myeloid cells 2 |
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Inserted expressed sequence, Humanized sequence) | Apoe | apolipoprotein E |
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Endonuclease-mediated (Humanized sequence) | App | amyloid beta (A4) precursor protein |
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Endonuclease-mediated (Humanized sequence) | Plcg2 | phospholipase C, gamma 2 |
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 Plcg2em3Adiuj homozygotes has not been assessed (February, 2020).
Expressed Gene | APOE, apolipoprotein E, human |
---|---|
Site of Expression | |
Site of Expression | |
Site of Expression |
Allele Name | endonuclease-mediated mutation 1, MODEL-AD Center |
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Allele Type | Endonuclease-mediated (Humanized sequence) |
Allele Synonym(s) | Jax R27H ki; Trem2 R47H KI |
Gene Symbol and Name | Trem2, triggering receptor expressed on myeloid cells 2 |
Gene Synonym(s) | |
Strain of Origin | C57BL/6J |
Chromosome | 17 |
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 Name | targeted mutation 1.1, MODEL-AD Center |
---|---|
Allele Type | Targeted (Inserted expressed sequence, Humanized sequence) |
Allele Synonym(s) | APOEepsilon4 |
Gene Symbol and Name | Apoe, apolipoprotein E |
Gene Synonym(s) | |
Expressed Gene | APOE, apolipoprotein E, human |
Strain of Origin | C57BL/6J |
Chromosome | 7 |
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 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. |
Allele Name | endonuclease-mediated mutation 3, MODEL-AD Center |
---|---|
Allele Type | Endonuclease-mediated (Humanized sequence) |
Allele Synonym(s) | |
Gene Symbol and Name | Plcg2, phospholipase C, gamma 2 |
Gene Synonym(s) | |
Strain of Origin | B6(SJL)-Apoetm1.1(APOE*4)Adiuj Trem2em1Adiuj/J |
Chromosome | 8 |
Molecular Note | The allele was generated by injecting cas9 nuclease and a single guide RNA designed to introduce a M28L point mutation. |
The viability/fertility of Plcg2em3Adiuj homozygotes has not been assessed (February, 2020).
Intercrossing animals homozygous for Apoetm1.1(APOE*4)Adiuj, Trem2em1Adiuj, and Appem1Adiuj, and heterozygous for Plcg2em3Adiuj with animals that are homozygous for Apoetm1.1(APOE*4)Adiuj, Trem2em1Adiuj, and Appem1Adiuj, and wildtype for Plcg2em3Adiuj is currently recommended.
homozygous for Apoetm1.1(APOE*4)Adiuj heterozygous for Plcg2em3Adiuj homozygous for Appem1Adiuj homozygous Trem2em1Adiuj 
OR
homozygous for Apoetm1.1(APOE*4)Adiuj wildtype for Plcg2em3Adiuj homozygous for Appem1Adiuj homozygous Trem2em1Adiuj 
When using the Plcg2*M28L/hAbeta/APOE4/Trem2*R47H mouse strain in a publication, please cite the originating article(s) and include JAX stock #034454 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Homozygous for Apoe<tm1.1(APOE*4)Adiuj>, heterozygous or wildtype for Plcg2<em3Adiuj>, homozygous or heterozygous for App<em1Adiuj>, and homozygous for Trem2<em1Adiuj> |
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