C57BL/6NCya-Fbxw7em1flox/Cya
Common Name:
Fbxw7-flox
Product ID:
S-CKO-11375
Background:
C57BL/6NCya
Product Type
Age
Genotype
Sex
Quantity
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Basic Information
Strain Name
Fbxw7-flox
Strain ID
CKOCMP-50754-Fbxw7-B6N-VA
Gene Name
Product ID
S-CKO-11375
Gene Alias
1110001A17Rik; AGO; Cdc4; Fbw7; Fbwd6; Fbx30; Fbxo30; Fbxw6; SEL-10
Background
C57BL/6NCya
NCBI ID
Modification
Conditional knockout
Chromosome
3
Phenotype
Document
Application
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Note: When using this mouse strain in a publication, please cite “C57BL/6NCya-Fbxw7em1flox/Cya mice (Catalog S-CKO-11375) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000107679
NCBI RefSeq
NM_001177773
Target Region
Exon 5
Size of Effective Region
~0.6 kb
Detailed Document
Overview of Gene Research
Fbxw7, also known as Sel10, hCDC4 or hAgo, is a member of the F-box protein family. It functions as the substrate recognition component of the SCF E3 ubiquitin ligase within the ubiquitin-proteasome system (UPS), which is involved in multiple cellular processes like cell cycle progression, differentiation, and survival [1,2]. By controlling proteasome-mediated degradation of oncoproteins such as cyclin E, c-Myc, Mcl-1, mTOR, Jun, Notch, and AURKA, Fbxw7 acts as a critical tumor suppressor [1].
In chondrocytes, mechanical overloading downregulates Fbxw7, leading to chondrocyte senescence and osteoarthritis development. Fbxw7 knockout in chondrocytes of mice induced chondrocyte senescence and accelerated cartilage catabolism, exacerbating osteoarthritis, while intra-articular injection of adenovirus-expressing Fbxw7 alleviated the condition. Mechanistically, mechanical overloading decreased Fbxw7 mRNA transcription and FBXW7-mediated MKK7 degradation, stimulating JNK signalling [3]. In myeloid cells, Fbxw7 deficiency protected mice from dextran sodium sulfate (DSS) and 2,6,4-trinitrobenzene sulfonic acid (TNBS) induced colitis. Fbxw7 deficiency led to decreased production of chemokines CCL2 and CCL7 by colonic CX3CR1hi resident macrophages and reduced accumulation of CX3CR1int pro-inflammatory mononuclear phagocytes in colitis colon tissue [4].
In conclusion, Fbxw7 is crucial for maintaining normal cellular functions through its role in the ubiquitin-proteasome system, especially in regulating the degradation of key oncoproteins. Mouse models with Fbxw7 knockout or knockdown have revealed its significance in diseases such as osteoarthritis and colitis, providing insights into the underlying molecular mechanisms and potential therapeutic targets [3,4].
References:
1. Yeh, Chien-Hung, Bellon, Marcia, Nicot, Christophe. 2018. FBXW7: a critical tumor suppressor of human cancers. In Molecular cancer, 17, 115. doi:10.1186/s12943-018-0857-2. https://pubmed.ncbi.nlm.nih.gov/30086763/
2. Fan, Jingyi, Bellon, Marcia, Ju, Mingyi, Fu, Liwu, Nicot, Christophe. 2022. Clinical significance of FBXW7 loss of function in human cancers. In Molecular cancer, 21, 87. doi:10.1186/s12943-022-01548-2. https://pubmed.ncbi.nlm.nih.gov/35346215/
3. Zhang, Haiyan, Shao, Yan, Yao, Zihao, Cai, Daozhang, Bai, Xiaochun. 2022. Mechanical overloading promotes chondrocyte senescence and osteoarthritis development through downregulating FBXW7. In Annals of the rheumatic diseases, 81, 676-686. doi:10.1136/annrheumdis-2021-221513. https://pubmed.ncbi.nlm.nih.gov/35058228/
4. He, Jia, Song, Yinjing, Li, Gaopeng, Lai, Lihua, Wang, Qingqing. 2019. Fbxw7 increases CCL2/7 in CX3CR1hi macrophages to promote intestinal inflammation. In The Journal of clinical investigation, 129, 3877-3893. doi:10.1172/JCI123374. https://pubmed.ncbi.nlm.nih.gov/31246581/
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