C57BL/6JCya-Ddb1em1flox/Cya
Common Name:
Ddb1-flox
Product ID:
S-CKO-02013
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
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Basic Information
Strain Name
Ddb1-flox
Strain ID
CKOCMP-13194-Ddb1-B6J-VA
Gene Name
Product ID
S-CKO-02013
Gene Alias
127kDa; p127-Ddb1
Background
C57BL/6JCya
NCBI ID
Modification
Conditional knockout
Chromosome
19
Phenotype
Document
Application
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Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Ddb1em1flox/Cya mice (Catalog S-CKO-02013) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000025649
NCBI RefSeq
NM_015735
Target Region
Exon 6~7
Size of Effective Region
~2.4 kb
Detailed Document
Overview of Gene Research
Ddb1, short for damage-specific DNA binding protein 1, is a crucial component of the Cullin-RING finger ligase family, specifically forming the CUL4-DDB1 ubiquitin ligase complex. This complex is involved in protein ubiquitination, a process that tags proteins for degradation or modulates their function, and is pivotal in regulating many cellular processes such as the cell cycle, DNA repair, and transcriptional regulation [5].
Adipose-or BAT-specific Ddb1 knockout mice exhibit severely whitened brown adipose tissue (BAT) and decreased expression of thermogenic genes. These mice develop hypothermia when acutely cold-exposed at 4 °C and partial lipodystrophy on a high-fat diet, indicating Ddb1's role in preparing brown adipocytes for cold-induced thermogenesis [4].
In the context of disease, Cul4A-DDB1-mediated monoubiquitination of phosphoglycerate dehydrogenase (PHGDH) promotes colorectal cancer metastasis. CUL4B-DDB1-COP1-mediated downregulation of UTX, a histone demethylase, advances colorectal cancer progression. Also, targeting CRL4 (CUL4A/DDB1) suppresses chemoresistant ovarian cancer growth by inducing mitophagy [1,2,3].
In summary, Ddb1 is essential for multiple cellular processes, with its function elucidated through gene knockout models. These models have revealed its significance in brown adipose tissue thermogenesis and its implications in cancer-related processes such as metastasis and chemoresistance, highlighting its potential as a therapeutic target in cancer and other related diseases.
References:
1. Zhang, Yajuan, Yu, Hua, Zhang, Jie, Li, Dawei, Yang, Weiwei. . Cul4A-DDB1-mediated monoubiquitination of phosphoglycerate dehydrogenase promotes colorectal cancer metastasis via increased S-adenosylmethionine. In The Journal of clinical investigation, 131, . doi:10.1172/JCI146187. https://pubmed.ncbi.nlm.nih.gov/34720086/
2. Luo, Dakui, Chen, Min, Li, Qingguo, Gao, Daming, Li, Xinxiang. 2023. CUL4B-DDB1-COP1-mediated UTX downregulation promotes colorectal cancer progression. In Experimental hematology & oncology, 12, 77. doi:10.1186/s40164-023-00440-z. https://pubmed.ncbi.nlm.nih.gov/37679762/
3. Meng, Yang, Qiu, Lei, Zeng, Xinyi, Zhang, Bo, Han, Junhong. 2022. Targeting CRL4 suppresses chemoresistant ovarian cancer growth by inducing mitophagy. In Signal transduction and targeted therapy, 7, 388. doi:10.1038/s41392-022-01253-y. https://pubmed.ncbi.nlm.nih.gov/36481655/
4. Wang, Xu, Liu, Shen-Ying, Hu, Guo-Sheng, Ye, Haobin, Zhao, Tong-Jin. 2022. DDB1 prepares brown adipocytes for cold-induced thermogenesis. In Life metabolism, 1, 39-53. doi:10.1093/lifemeta/loac003. https://pubmed.ncbi.nlm.nih.gov/39872690/
5. Raisch, Jennifer, Dubois, Marie-Line, Groleau, Marika, Jacques, Pierre-Étienne, Boisvert, François-Michel. 2023. Pulse-SILAC and Interactomics Reveal Distinct DDB1-CUL4-Associated Factors, Cellular Functions, and Protein Substrates. In Molecular & cellular proteomics : MCP, 22, 100644. doi:10.1016/j.mcpro.2023.100644. https://pubmed.ncbi.nlm.nih.gov/37689310/
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