C57BL/6JCya-Fbxl12em1flox/Cya
Common Name:
Fbxl12-flox
Product ID:
S-CKO-10217
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
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Basic Information
Strain Name
Fbxl12-flox
Strain ID
CKOCMP-30843-Fbxl12-B6J-VA
Gene Name
Product ID
S-CKO-10217
Gene Alias
3110048D16Rik; Fbl12
Background
C57BL/6JCya
NCBI ID
Modification
Conditional knockout
Chromosome
9
Phenotype
Document
Application
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Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Fbxl12em1flox/Cya mice (Catalog S-CKO-10217) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000151861
NCBI RefSeq
NM_001286529
Target Region
Exon 3
Size of Effective Region
~2.6 kb
Detailed Document
Overview of Gene Research
Fbxl12, an F-box and leucine-rich repeat protein, is a component of the Skp1-Cul1-F box (SCF) E3 ubiquitin ligase complex. It plays crucial roles in multiple biological processes such as cell cycle regulation, differentiation, and DNA damage response [3,5,6]. It is involved in pathways like Fanconi anemia (FA) signaling, which is a key genomic maintenance pathway activated in response to replication stress [1].
In mouse models, FBXL12-null mice showed a differentiation block at the CD4⁺ CD8⁺ (DP)-CD4⁺ CD8⁻ or CD4⁻ CD8⁺ (SP) transition during T-cell differentiation, associated with ALDH3 accumulation in DP cells, indicating its cell-autonomous role in thymocyte maturation [4]. Most mice deficient in FBXL12 died during the embryonic or perinatal period due to abnormal placental development, with impaired formation of the junctional zone and ALDH3 accumulation in the placenta, highlighting its importance in trophoblast differentiation during placental development [2]. Depletion of FBXL12 exacerbated oncogene-induced replication stress and sensitized cancer cells to drug-induced replication stress by WEE1 inhibition, suggesting its potential as a therapeutic target in CYCLIN E-overexpressing cancers [1].
In conclusion, Fbxl12 is essential for T-cell and trophoblast differentiation, and plays a role in regulating replication recovery under stress conditions. The study of Fbxl12 knockout mouse models has provided insights into its functions in placental development and T-cell maturation, as well as its potential as a therapeutic target in certain cancers.
References:
1. Brunner, Andrä, Li, Qiuzhen, Fisicaro, Samuele, Orre, Lukas M, Sangfelt, Olle. 2023. FBXL12 degrades FANCD2 to regulate replication recovery and promote cancer cell survival under conditions of replication stress. In Molecular cell, 83, 3720-3739.e8. doi:10.1016/j.molcel.2023.07.026. https://pubmed.ncbi.nlm.nih.gov/37591242/
2. Nishiyama, Masaaki, Nita, Akihiro, Yumimoto, Kanae, Nakayama, Keiichi I. 2015. FBXL12-Mediated Degradation of ALDH3 is Essential for Trophoblast Differentiation During Placental Development. In Stem cells (Dayton, Ohio), 33, 3327-40. doi:10.1002/stem.2088. https://pubmed.ncbi.nlm.nih.gov/26124079/
3. Mallampalli, Rama K, Kaercher, Leah, Snavely, Courtney, Zhao, Jing, Agassandian, Marianna. 2013. Fbxl12 triggers G1 arrest by mediating degradation of calmodulin kinase I. In Cellular signalling, 25, 2047-59. doi:10.1016/j.cellsig.2013.05.012. https://pubmed.ncbi.nlm.nih.gov/23707388/
4. Nita, Akihiro, Nishiyama, Masaaki, Muto, Yoshiharu, Nakayama, Keiichi I. 2016. FBXL12 regulates T-cell differentiation in a cell-autonomous manner. In Genes to cells : devoted to molecular & cellular mechanisms, 21, 517-24. doi:10.1111/gtc.12360. https://pubmed.ncbi.nlm.nih.gov/26999371/
5. Postow, Lisa, Funabiki, Hironori. 2013. An SCF complex containing Fbxl12 mediates DNA damage-induced Ku80 ubiquitylation. In Cell cycle (Georgetown, Tex.), 12, 587-95. doi:10.4161/cc.23408. https://pubmed.ncbi.nlm.nih.gov/23324393/
6. Tsuruta, Fuminori, Kim, Jaehyun, Fukuda, Tomomi, Kigoshi, Yu, Chiba, Tomoki. 2015. The intronic region of Fbxl12 functions as an alternative promoter regulated by UV irradiation. In Biochemistry and biophysics reports, 3, 100-107. doi:10.1016/j.bbrep.2015.07.010. https://pubmed.ncbi.nlm.nih.gov/29124172/
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