CB2 is normally up-regulated following pro-inflammatory and nociceptive stimuli, and in human brain tissues affected by Alzheimer's disease (AD), multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). These CB2 knockout mice (CB2-, CB2R- or Cnr2-) may be useful for studying these diseases, pain management and drug/antibody therapeutics.Read More +
Cannabinoid receptor 2 (CB2 or CB2R) is normally expressed in cells of the haematopoietic lineage, central nervous system and bone. In immune cells, CB2 is expressed on leukocytes and localized in intracellular membranous structures. Endogenous expression is up-regulated by pro-inflammatory and nociceptive stimuli. CB2 activation reduces expression of adhesion molecules in brain endothelium, decreasing leukocyte engagement and recruitment.
In these CB2 knockout mice (CB2-/-, CB2R-/-, Cnr2-/- or Cnr2tm1Dgen), CB2 agonists have no effect on minimizing leukocyte-endothelial cell interaction. After treatment with lipopolysaccharide (LPS), CB2 null mice fail to show complete resolution of inflammation compared to wild type controls. An increase in leukocyte adhesion is seen when Cnr2-/- leukocytes are transferred into wildtype recipient mice.
This CB2 knockout mutant was created and characterized by Deltagen, Inc. View phenotypic data developed by Deltagen.
J20 transgenic amyloid mice express the K670N/M671L/V717F mutant form of amyloid precursor protein under control of the human platelet–derived growth factor β polypeptide promoter (Stock No. 006293). Hemizygous J20 mice are a Familial Alzheimer's Disease model with progressive amyloid deposition as they age (significant reactive microgliosis by 8 months of age). C57BL/6 mice homozygous for Cnr2tm1Dgen and also harboring the J20 transgene (J20 CNR2/-/) exhibit increased amyloid pathology (increased soluble Aβ42, plaque deposition and plaque associated microglia), but altered tau processing (suppressed total tau), when compared to J20 mice alone.
Of note, another published CB2 knockout allele (Cnr2tm1Zim) has been used to show CB2-deficient macrophages are resistant to the inhibitory effects of δ-9 tetrahydrocannabinol (THC) and CB2 knockout mice have increased severity in experimental autoimmune encephalitis. Homozygous Cnr2tm1Zim mice also harboring the R6/2 transgene (encoding human mutant Huntington exon 1) have increased microglial activation and exacerbated Huntington disease progression/excitotoxicity compared to R6/2 mice alone.
The CB2 knockout allele (CB2-, CB2R-, Cnr2- or Cnr2tm1Dgen) was created by Deltagen. Specifically, the "Neo555T" construct was electroporated into 129P2/OlaHsd-derived E14 embryonic stem (ES) cells. Targeted mutant cell line 655 had homologous recombination of the "Neo555T" construct resulting in a 334 bp deletion in the coding exon of cannabinoid receptor 2 [macrophage] locus (CB2; Cnr2) on chromosome 4. The donating investigator reported the Cnr2- mice were backcrossed at least five generations to C57BL/6 mice (see SNP note below) prior to sending to The Jackson Laboratory Repository.
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 2 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.
|Allele Name||targeted mutation 1, Deltagen|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Cnr2, cannabinoid receptor 2 (macrophage)|
|Strain of Origin||129P2/OlaHsd|
|Molecular Note||This gene was disrupted by homologous recombination. Normally, RNA transcripts are detectable in lung, liver, thymus, spleen, lymph nodes, bone marrow, skin and testis.|
When maintaining a live colony, heterozygous or homozygous mice may be bred together.
When using the CB2R KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #005786 in your Materials and Methods section.
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