C57BL/6JCya-D2hgdhem1/Cya
Common Name:
D2hgdh-KO
Product ID:
S-KO-17753
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
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Basic Information
Strain Name
D2hgdh-KO
Strain ID
KOCMP-98314-D2hgdh-B6J-VB
Gene Name
Product ID
S-KO-17753
Gene Alias
-
Background
C57BL/6JCya
NCBI ID
Modification
Conventional knockout
Chromosome
1
Phenotype
Document
Application
--
Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-D2hgdhem1/Cya mice (Catalog S-KO-17753) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000112881
NCBI RefSeq
NM_001310767
Target Region
Exon 3
Size of Effective Region
~1.0 kb
Detailed Document
Overview of Gene Research
D2hgdh, encoding D-2-hydroxyglutarate dehydrogenase, is an inducible enzyme that converts D-2-hydroxyglutarate (D2HG) into the endogenous metabolite 2-oxoglutarate [1]. It is involved in regulating cellular energy and biosynthetic intermediates, and is associated with pathways related to α-ketoglutarate-dependent dioxygenases, which are implicated in histone and DNA methylation, and HIF1α hydroxylation [2].
In the context of immunotherapy, D2HG impairs CD8 T lymphocyte function, but D2HGDH-modified CAR-T cells show distinct phenotypes. D2HGDH-over-expression (OE) CAR-T cells can utilize D2HG catabolism to enhance T cell expansion, function, and anti-tumor effectiveness in an immunosuppressive microenvironment [1]. In diffuse large B-cell lymphoma, D2HGDH mutants are enzymatically inert, while wild-type D2HGDH elevates α-ketoglutarate levels, influencing epigenetic modifications [2]. Downregulating D2HGDH in neurons reduces the glutathione reduced (GSH)/glutathione oxidized (GSSG) ratio, elevates reactive oxygen species (ROS) levels, affects synaptic function, and enhances susceptibility to epilepsy [3].
In conclusion, D2hgdh is crucial for D2HG catabolism and regulation of α-ketoglutarate levels, influencing multiple biological processes. Studies on D2hgdh-modified CAR-T cells, its mutants in lymphoma, and its downregulation in epilepsy-related neurons highlight its significance in immunotherapy, cancer, and epilepsy research, providing potential therapeutic targets for these diseases.
References：
1. Yang, Quanjun, Hao, Juan, Chi, Mengyi, Zheng, Shuier, Guo, Cheng. 2022. D2HGDH-mediated D2HG catabolism enhances the anti-tumor activities of CAR-T cells in an immunosuppressive microenvironment. In Molecular therapy : the journal of the American Society of Gene Therapy, 30, 1188-1200. doi:10.1016/j.ymthe.2022.01.007. https://pubmed.ncbi.nlm.nih.gov/35007759/
2. Lin, An-Ping, Abbas, Saman, Kim, Sang-Woo, Dahia, Patricia L M, Aguiar, Ricardo C T. 2015. D2HGDH regulates alpha-ketoglutarate levels and dioxygenase function by modulating IDH2. In Nature communications, 6, 7768. doi:10.1038/ncomms8768. https://pubmed.ncbi.nlm.nih.gov/26178471/
3. Zhang, Zhijuan, Zhang, Hui, Zhang, Peng, Ma, Yuanlin, Kwan, Patrick. 2024. D2HGDH Deficiency Regulates Seizures through GSH/Prdx6/ROS-Mediated Excitatory Synaptic Activity. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 12, e2404488. doi:10.1002/advs.202404488. https://pubmed.ncbi.nlm.nih.gov/39739583/
Quality Control Standard
Sperm Test
Pre-cryopreservation: Measurement of sperm concentration, determination of sperm viability.
Post-cryopreservation: A vial of cryopreserved sperms is selected for in-vitro fertilization from each batch.
Environmental Standards:SPF
Available Region:Global
Source:Cyagen