This CRISPR/Cas9 generated mutant of the Trem2 gene carries the Y38C point mutation which has been shown to increase Alzheimer's disease risk.
Bruce Lamb, Indiana University School of Medicine
This CRISPR/Cas9-generated knock-out mutant of the Trem2, triggering receptor expressed on myeloid cells 2, gene introduces a Y38C point mutation. The targeted Trem2 gene encodes a protein that is part of a receptor signaling complex with TYRO protein tyrosine kinase binding protein, and that activates macrophages and dendritic cells during immune responses. Loss-of-function variants of the TREM2 gene are associated with Alzheimer's Disease. Homozygotes are viable and fertile. As the mice are characterized, we will modify the strain description and add phenotype data.
Plasmids encoding cas9 nuclease, an oglionucleotide with the desired mutation and a single guide RNA designed to introduce a Y38C point mutation into the Trem2 gene were introduced into the cytoplasm C57BL/6J-derived fertilized eggs with well recognized pronuclei. Correctly targeted embryos were transferred to pseudopregnant females. Pups containing the engineered mutations were identified by sequencing and PCR and further bred to C57BL/6J (Stock No. 000664) for 3 generations to develop the colony. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).
|Allele Name||endonuclease-mediated mutation 3, MODEL-AD Center|
|Allele Type||Endonuclease-mediated (Humanized sequence)|
|Allele Synonym(s)||Trem2 Y38C KI|
|Gene Symbol and Name||Trem2, triggering receptor expressed on myeloid cells 2|
|Strain of Origin||C57BL/6J|
|Molecular Note||The allele was generated by injecting cas9 nuclease and a single guide RNA designed to introduce a Y38C point mutation into the gene.|
When maintaining a live colony, these mice can be bred as homozygotes. Homozygotes are viable and fertile. As the mice are characterized, we will modify the strain description if necessary and add data related to viability and fertility.
When using the Trem2 Y38C KI (Trem2*Y38C) mouse strain in a publication, please cite the originating article(s) and include JAX stock #029725 in your Materials and Methods section.