C57BL/6JCya-Insig1em1flox/Cya
Common Name:
Insig1-flox
Product ID:
S-CKO-07426
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
Quantity
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Basic Information
Strain Name
Insig1-flox
Strain ID
CKOCMP-231070-Insig1-B6J-VA
Gene Name
Product ID
S-CKO-07426
Gene Alias
1810013C12Rik; Insig-1
Background
C57BL/6JCya
NCBI ID
Modification
Conditional knockout
Chromosome
5
Phenotype
Document
Application
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Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Insig1em1flox/Cya mice (Catalog S-CKO-07426) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000059155
NCBI RefSeq
NM_153526
Target Region
Exon 2
Size of Effective Region
~1.3 kb
Detailed Document
Overview of Gene Research
Insig1, or insulin-induced gene 1, is an endoplasmic reticulum-resident protein that plays a crucial role in regulating intracellular cholesterol and fatty acid synthesis. It is part of a complex with SREBP cleavage-activating protein (SCAP) and sterols, which inhibits sterol regulatory element-binding proteins (SREBPs) [1,3,4,5,6,7]. This regulation of SREBPs is essential for lipid metabolism, and dysregulation can lead to various metabolic disorders.
In cancer, studies have shown significant roles of Insig1. In human hepatocellular carcinoma (HCC), phosphorylated PCK1 translocates to the endoplasmic reticulum and phosphorylates Insig1, disrupting the Insig-SCAP interaction, activating SREBPs, and promoting lipogenesis, tumor cell proliferation, and tumorigenesis. Phosphorylation of Insig1 at Ser207 is associated with poor HCC prognosis [1]. In colorectal cancer, a hypoxia-responsive circRNA named circINSIG1 encodes a protein that promotes ubiquitin-dependent degradation of Insig1, reprogramming cholesterol metabolism to enhance CRC proliferation and metastasis [2]. In esophageal squamous cell carcinoma, LPCAT1 activates EGFR, leading to down-regulation of Insig-1 expression, facilitating SREBP-1 entry into the nucleus to promote cholesterol synthesis and cancer progression [7]. In non-alcoholic fatty liver disease (NAFLD), miR-363-3p targets Insig1, promoting SREBP cleavage and nuclear translocation, leading to lipid accumulation, and apigenin alleviates NAFLD by regulating the miR-363-3p/Insig1/SREBP1 pathway [4].
In conclusion, Insig1 is a key regulator in lipid metabolism-related pathways. Its dysregulation is associated with multiple diseases, especially cancers and metabolic disorders. Studies using gene-related models, though not specifically KO/CKO mouse models in the provided references, have revealed its significance in disease-related biological processes. Understanding Insig1's functions can potentially provide new therapeutic targets for treating these diseases.
References:
1. Xu, Daqian, Wang, Zheng, Xia, Yan, Hung, Mien-Chie, Lu, Zhimin. 2020. The gluconeogenic enzyme PCK1 phosphorylates INSIG1/2 for lipogenesis. In Nature, 580, 530-535. doi:10.1038/s41586-020-2183-2. https://pubmed.ncbi.nlm.nih.gov/32322062/
2. Xiong, Li, Liu, Hua-Shan, Zhou, Chi, Kang, Liang, Liang, Zhen-Xing. 2023. A novel protein encoded by circINSIG1 reprograms cholesterol metabolism by promoting the ubiquitin-dependent degradation of INSIG1 in colorectal cancer. In Molecular cancer, 22, 72. doi:10.1186/s12943-023-01773-3. https://pubmed.ncbi.nlm.nih.gov/37087475/
3. Xu, Yingying, Tao, Jiawang, Yu, Xiaorui, Lin, Xianhua, Li, Yin-Xiong. 2021. Hypomorphic ASGR1 modulates lipid homeostasis via INSIG1-mediated SREBP signaling suppression. In JCI insight, 6, . doi:10.1172/jci.insight.147038. https://pubmed.ncbi.nlm.nih.gov/34622799/
4. Wang, Lechen, Jia, Guotao, Fu, Rongrong, Zhang, Min, Meng, Jing. 2024. Hepatic miR-363 promotes nonalcoholic fatty liver disease by suppressing INSIG1. In The Journal of nutritional biochemistry, 134, 109717. doi:10.1016/j.jnutbio.2024.109717. https://pubmed.ncbi.nlm.nih.gov/39103107/
5. Cheng, Chunming, Ru, Peng, Geng, Feng, Chakravarti, Arnab, Guo, Deliang. . Glucose-Mediated N-glycosylation of SCAP Is Essential for SREBP-1 Activation and Tumor Growth. In Cancer cell, 28, 569-581. doi:10.1016/j.ccell.2015.09.021. https://pubmed.ncbi.nlm.nih.gov/26555173/
6. Watanabe, Yuichi, Sasaki, Takashi, Miyoshi, Shoko, Yamauchi, Yoshio, Sato, Ryuichiro. 2021. Insulin-induced genes INSIG1 and INSIG2 mediate oxysterol-dependent activation of the PERK-eIF2α-ATF4 axis. In The Journal of biological chemistry, 297, 100989. doi:10.1016/j.jbc.2021.100989. https://pubmed.ncbi.nlm.nih.gov/34298014/
7. Tao, Mingyue, Luo, Jing, Gu, Tong, Luo, Chao, Wang, Qilong. 2021. LPCAT1 reprogramming cholesterol metabolism promotes the progression of esophageal squamous cell carcinoma. In Cell death & disease, 12, 845. doi:10.1038/s41419-021-04132-6. https://pubmed.ncbi.nlm.nih.gov/34518524/
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