C57BL/6JCya-Dhodhem1/Cya
Common Name:
Dhodh-KO
Product ID:
S-KO-10933
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
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Basic Information
Strain Name
Dhodh-KO
Strain ID
KOCMP-56749-Dhodh-B6J-VA
Gene Name
Product ID
S-KO-10933
Gene Alias
2810417D19Rik
Background
C57BL/6JCya
NCBI ID
Modification
Conventional knockout
Chromosome
8
Phenotype
Document
Application
--
Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Dhodhem1/Cya mice (Catalog S-KO-10933) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000123605
NCBI RefSeq
NM_020046
Target Region
Exon 3
Size of Effective Region
~1.4 kb
Detailed Document
Overview of Gene Research
Dihydroorotate dehydrogenase (DHODH) is the rate-limiting enzyme in de novo pyrimidine nucleotide biosynthesis [3]. It plays a crucial role in maintaining normal cellular function as pyrimidine nucleotides are essential for DNA and RNA synthesis, cell cycle progression, and other key biological processes [4].
In cancer research, inactivation of DHODH has shown significant effects. In GPX4low cancer cells, it induces extensive mitochondrial lipid peroxidation and ferroptosis, a form of regulated cell death induced by excessive lipid peroxidation [1]. Moreover, in glioblastoma, depletion of PRR11, which binds to and stabilizes DHODH, sensitizes GBM cells to temozolomide by inducing ferroptosis, indicating a role of the PRR11-DHODH axis in ferroptosis-and temozolomide-resistance [2]. In T-cell acute lymphoblastic leukemia, small molecule inhibition of DHODH leads to intracellular nucleotide starvation, inhibiting DNA and RNA synthesis, causing cell cycle arrest and death [4].
In conclusion, DHODH is essential for de novo pyrimidine nucleotide biosynthesis and normal cellular function. Its inactivation in various disease models, especially in cancer, reveals its potential as a therapeutic target. Studies on DHODH in cancer, such as in glioblastoma and T-cell acute lymphoblastic leukemia, suggest that targeting DHODH could offer new treatment strategies for these diseases [1,2,4].
References:
1. Mao, Chao, Liu, Xiaoguang, Zhang, Yilei, Olszewski, Kellen, Gan, Boyi. 2021. DHODH-mediated ferroptosis defence is a targetable vulnerability in cancer. In Nature, 593, 586-590. doi:10.1038/s41586-021-03539-7. https://pubmed.ncbi.nlm.nih.gov/33981038/
2. Miao, Zong, Xu, Lei, Gu, Wei, Ji, Jing, Chen, Juxiang. 2024. A targetable PRR11-DHODH axis drives ferroptosis- and temozolomide-resistance in glioblastoma. In Redox biology, 73, 103220. doi:10.1016/j.redox.2024.103220. https://pubmed.ncbi.nlm.nih.gov/38838551/
3. Amos, Alvan, Amos, Alex, Wu, Lirong, Xia, He. 2023. The Warburg effect modulates DHODH role in ferroptosis: a review. In Cell communication and signaling : CCS, 21, 100. doi:10.1186/s12964-022-01025-9. https://pubmed.ncbi.nlm.nih.gov/37147673/
4. Sexauer, Amy N, Alexe, Gabriela, Gustafsson, Karin, Stegmaier, Kimberly, Sykes, David B. . DHODH: a promising target in the treatment of T-cell acute lymphoblastic leukemia. In Blood advances, 7, 6685-6701. doi:10.1182/bloodadvances.2023010337. https://pubmed.ncbi.nlm.nih.gov/37648673/
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