C57BL/6JCya-Wdr24em1flox/Cya
Common Name:
Wdr24-flox
Product ID:
S-CKO-17731
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
Quantity
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Basic Information
Strain Name
Wdr24-flox
Strain ID
CKOCMP-268933-Wdr24-B6J-VC
Gene Name
Product ID
S-CKO-17731
Gene Alias
-
Background
C57BL/6JCya
NCBI ID
Modification
Conditional knockout
Chromosome
17
Phenotype
Document
Application
--
Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Wdr24em1flox/Cya mice (Catalog S-CKO-17731) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000026833
NCBI RefSeq
NM_173741
Target Region
Exon 2~3
Size of Effective Region
~1.4 kb
Detailed Document
Overview of Gene Research
Wdr24 is an essential component of the GATOR2 complex. The GATOR2 complex is key in linking amino acid signals to the mTORC1 pathway, which is a central regulator of metabolism and cell growth [1,2,3,4,5,6,7,8,9,10]. By being part of GATOR2, Wdr24 is involved in processes like nutrient sensing, and its function is crucial for normal cell growth and metabolism. Genetic models, such as mouse models, have been valuable in studying Wdr24's functions.
In phosphomimetic Wdr24S155D knock-in mice, there is early embryonic lethality and reduced mTORC1 activity, while phospho-deficient Wdr24S155A knock-in mice are more resistant to fasting and display elevated mTORC1 activity. This shows that AMPK-mediated phosphorylation of Wdr24 at S155 modulates glucose-induced mTORC1 activation [2]. In addition, Wdr24 ablation in mice leads to severe growth defects and embryonic lethality at E10.5, indicating that Wdr24 is essential for transmitting amino acid availability to mTORC1 during embryonic development [4].
In conclusion, Wdr24, as a part of the GATOR2 complex, is vital for regulating mTORC1 activity in response to nutrient signals such as amino acids and glucose. The study of Wdr24 using gene knockout mouse models has revealed its significance in embryonic development and metabolism-related processes. These findings have implications for understanding diseases where mTORC1 signaling is aberrantly activated, like certain cancers [1,2,4,8,9].
References:
1. Yin, Shasha, Liu, Liu, Ball, Lauren E, Wang, Haizhen, Gan, Wenjian. 2023. CDK5-PRMT1-WDR24 signaling cascade promotes mTORC1 signaling and tumor growth. In Cell reports, 42, 112316. doi:10.1016/j.celrep.2023.112316. https://pubmed.ncbi.nlm.nih.gov/36995937/
2. Dai, Xiaoming, Jiang, Cong, Jiang, Qiwei, Guo, Jianping, Wei, Wenyi. 2023. AMPK-dependent phosphorylation of the GATOR2 component WDR24 suppresses glucose-mediated mTORC1 activation. In Nature metabolism, 5, 265-276. doi:10.1038/s42255-022-00732-4. https://pubmed.ncbi.nlm.nih.gov/36732624/
3. Valenstein, Max L, Rogala, Kacper B, Lalgudi, Pranav V, Quast, Jan-Philipp, Sabatini, David M. 2022. Structure of the nutrient-sensing hub GATOR2. In Nature, 607, 610-616. doi:10.1038/s41586-022-04939-z. https://pubmed.ncbi.nlm.nih.gov/35831510/
4. Jiang, Cong, Dai, Xiaoming, He, Shaohui, Xiao, Jianru, Wei, Wenyi. 2022. Ring domains are essential for GATOR2-dependent mTORC1 activation. In Molecular cell, 83, 74-89.e9. doi:10.1016/j.molcel.2022.11.021. https://pubmed.ncbi.nlm.nih.gov/36528027/
5. Wolfson, Rachel L, Chantranupong, Lynne, Saxton, Robert A, Cantor, Jason R, Sabatini, David M. 2015. Sestrin2 is a leucine sensor for the mTORC1 pathway. In Science (New York, N.Y.), 351, 43-8. doi:10.1126/science.aab2674. https://pubmed.ncbi.nlm.nih.gov/26449471/
6. Yan, Guokai, Yang, Jinxin, Li, Wen, Guan, Jialiang, Liu, Ying. 2023. Genome-wide CRISPR screens identify ILF3 as a mediator of mTORC1-dependent amino acid sensing. In Nature cell biology, 25, 754-764. doi:10.1038/s41556-023-01123-x. https://pubmed.ncbi.nlm.nih.gov/37037994/
7. Bar-Peled, Liron, Chantranupong, Lynne, Cherniack, Andrew D, Meyerson, Matthew, Sabatini, David M. . A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1. In Science (New York, N.Y.), 340, 1100-6. doi:10.1126/science.1232044. https://pubmed.ncbi.nlm.nih.gov/23723238/
8. Cheng, Hongyu, Ji, Zhe, Wang, Yang, Yang, Hua, Ge, Baoxue. 2024. Mycobacterium tuberculosis produces D-serine under hypoxia to limit CD8+ T cell-dependent immunity in mice. In Nature microbiology, 9, 1856-1872. doi:10.1038/s41564-024-01701-1. https://pubmed.ncbi.nlm.nih.gov/38806671/
9. Solanki, Sumeet, Sanchez, Katherine, Ponnusamy, Varun, Lee, Jun Hee, Shah, Yatrik M. 2022. Dysregulated Amino Acid Sensing Drives Colorectal Cancer Growth and Metabolic Reprogramming Leading to Chemoresistance. In Gastroenterology, 164, 376-391.e13. doi:10.1053/j.gastro.2022.11.014. https://pubmed.ncbi.nlm.nih.gov/36410445/
10. Cai, Weili, Wei, Youheng, Jarnik, Michal, Reich, John, Lilly, Mary A. 2016. The GATOR2 Component Wdr24 Regulates TORC1 Activity and Lysosome Function. In PLoS genetics, 12, e1006036. doi:10.1371/journal.pgen.1006036. https://pubmed.ncbi.nlm.nih.gov/27166823/
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