These floxed mutant mice possess loxP sites flanking exons 2 and 3 of the Trem2 gene. This strain may be useful for generating conditional mutations in applications related to Alzheimer's Disease.
Bruce Lamb, Indiana University School of Medicine
Guixiang Xu, Indiana University School of Medicine
Adrian Oblak, Indiana University School of Medicine, Alzheimer Disease Center
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. These mice possess loxP sites on either side of exons 2 and 3 of the targeted gene.
The donating investigator reports that homozygotes are viable and fertile. As the mice are characterized, we will modify the strain description and add phenotype data.
When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exons 2 and 3 deleted in the cre-expressing tissues.
A targeting vector containing (3’ to 5’): FRT site, lacZ, polyadenylation signal, loxP site, neomycin resistance gene under the control of the human beta-actin promoter, SV40 polyA, FRT site, loxP site, was inserted upstream of exon 2 of the targeted gene, and another loxP site was inserted upstream of exon 4. This construct was electroporated into C57BL/6N-Atm1Brd derived JM8A3.N1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The mice were then crossed to strain expressing FLP recombinase under the control of the Pgk1 promoter (Stock No. 011065) to excise the lacZ and neo cassettes, generating a "conditional ready" (floxed) allele with exons 2 and 3 flanked by loxP sites.
The mice were then crossed to C57BL/6J for 4 generations, and no longer carry the FLP recombinase transgene.
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||targeted mutation 1c, Wellcome Trust Sanger Institute|
|Allele Type||Targeted (Conditional ready (e.g. floxed))|
|Gene Symbol and Name||Trem2, triggering receptor expressed on myeloid cells 2|
|Strain of Origin||C57BL/6N-Atm1Brd|
|Molecular Note||The L1L2_Bact_P cassette was inserted at position 48236393 of Chromosome 17 upstream of exon 2 (Build GRCm38). The cassette is composed of an FRT site followed by lacZ sequence and a loxP site. This first loxP site is followed by neomycin resistance gene under the control of the human beta-actin promoter, SV40 polyA, a second FRT site and a second loxP site. A third loxP site is inserted upstream of exon 4 at position 48237757. A "conditional ready" (floxed) allele is created by flp recombinase expression in mice carrying this allele.|
When maintaining a live colony, these mice can be bred as heterozygotes or homozygotes. The donating investigator reports that homozygotes are viable and fertile.
When using the Trem2 flox mouse strain in a publication, please cite the originating article(s) and include JAX stock #029853 in your Materials and Methods section.