C57BL/6JCya-Gigyf2em1/Cya
Common Name:
Gigyf2-KO
Product ID:
S-KO-06076
Background:
C57BL/6JCya
Product Type
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Genotype
Sex
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Basic Information
Strain Name
Gigyf2-KO
Strain ID
KOCMP-227331-Gigyf2-B6J-VA
Gene Name
Product ID
S-KO-06076
Gene Alias
2610016F01Rik; A830080H02Rik; Tnrc15; mKIAA0642
Background
C57BL/6JCya
NCBI ID
Modification
Conventional knockout
Chromosome
1
Phenotype
Document
Application
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Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Gigyf2em1/Cya mice (Catalog S-KO-06076) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000027475
NCBI RefSeq
NM_146112
Target Region
Exon 6
Size of Effective Region
~1.0 kb
Detailed Document
Overview of Gene Research
Gigyf2, or Grb10-interacting GYF protein 2, is an RNA-binding protein with diverse functions. It is involved in multiple biological processes such as translation regulation, with implications in pathways like mTORC1-S6K1 signaling. It has significance in various biological contexts, including neural development, and its malfunction is associated with aging-related diseases [1,2,3]. Genetic models, like KO/CKO mouse models, are valuable for studying its functions.
In endothelial cells, aberrant hyperexpression of Gigyf2 was found in senescent human ECs and aortas of old mice. Silencing Gigyf2 in senescent ECs suppressed eNOS-uncoupling, senescence, and endothelial dysfunction. Conversely, overexpressing it in non-senescent cells promoted these processes and activated the mTORC1-S6K1 pathway, which could be blocked by rapamycin or N-Acetyl-l-cysteine. Transcriptome analysis showed that staufen double-stranded RNA binding protein 1 (STAU1) was downregulated in Gigyf2-depleted ECs, and STAU1 depletion attenuated Gigyf2-induced cellular senescence, dysfunction, and inflammation in young ECs. Also, Gigyf2 enhanced STAU1 mRNA stability, and STAU1 upregulated LAMTOR4 expression by binding to its intron region, leading to mTORC1 activation and ultimately EC senescence, dysfunction, and vascular aging. In the mice model, Gigyf2flox/flox Cdh-Cre+ mice protected aged mice from aging-associated vascular endothelium-dependent relaxation and arterial stiffness [1]. In the context of hepatic insulin resistance, high-fat diet-induced IR in mice was alleviated by Gigyf2 knockdown. In vitro, high levels of palmitic acid exposure in HepG2 cells increased Gigyf2 expression, and silencing Gigyf2 ameliorated IR. Gigyf2 overexpression promoted IR through up-regulating STAU1/PTEN and inactivating the PI3K/AKT pathway. STAU1 stabilized PTEN mRNA by binding to its 3'UTR [4].
In conclusion, Gigyf2, as an RNA-binding protein, is crucial in regulating translation, endothelial cell senescence, and insulin resistance. The findings from Gigyf2-related KO/CKO mouse models and in vitro cell experiments contribute to understanding its role in vascular aging and obesity-related metabolic diseases like type 2 diabetes, suggesting it as a potential therapeutic target for these conditions [1,4].
References:
1. Niu, Fanglin, Li, Zhuozhuo, Ren, Yuanyuan, Yu, Yi, Xiong, Yuyan. 2023. Aberrant hyper-expression of the RNA binding protein GIGYF2 in endothelial cells modulates vascular aging and function. In Redox biology, 65, 102824. doi:10.1016/j.redox.2023.102824. https://pubmed.ncbi.nlm.nih.gov/37517320/
2. Hickey, Kelsey L, Dickson, Kimberley, Cogan, J Zachery, Weissman, Jonathan S, Kostova, Kamena K. 2020. GIGYF2 and 4EHP Inhibit Translation Initiation of Defective Messenger RNAs to Assist Ribosome-Associated Quality Control. In Molecular cell, 79, 950-962.e6. doi:10.1016/j.molcel.2020.07.007. https://pubmed.ncbi.nlm.nih.gov/32726578/
3. Yang, Wanchun, Yuan, Qiuyun, Zhang, Shuxin, Chen, Mina, Liu, Yanhui. 2021. Elevated GIGYF2 expression suppresses tumor migration and enhances sensitivity to temozolomide in malignant glioma. In Cancer gene therapy, 29, 750-757. doi:10.1038/s41417-021-00353-1. https://pubmed.ncbi.nlm.nih.gov/34059782/
4. Lv, Ziwei, Ren, Yuanyuan, Li, Yang, Xiong, Yuyan, Qian, Lu. 2024. RNA-binding protein GIGYF2 orchestrates hepatic insulin resistance through STAU1/PTEN-mediated disruption of the PI3K/AKT signaling cascade. In Molecular medicine (Cambridge, Mass.), 30, 124. doi:10.1186/s10020-024-00889-6. https://pubmed.ncbi.nlm.nih.gov/39138413/
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