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).

The use of this mouse model is subject to the terms and conditions of the Limited Use Label License from Caribou Biosciences, Inc.

The use of this mouse strain or other product (the "Licensed Product") is subject to the terms and conditions of the Limited License from The Broad Institute.

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. <a href="https://www.jax.org/strain/030670">030670</a>) 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.

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