C57BL/6JCya-Xbp1em1/Cya
Common Name:
Xbp1-KO
Product ID:
S-KO-05805
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
Quantity
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Basic Information
Strain Name
Xbp1-KO
Strain ID
KOCMP-22433-Xbp1-B6J-VA
Gene Name
Product ID
S-KO-05805
Gene Alias
D11Ertd39e; TREB-5; TREB5; XBP-1
Background
C57BL/6JCya
NCBI ID
Modification
Conventional knockout
Chromosome
11
Phenotype
Document
Application
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Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Xbp1em1/Cya mice (Catalog S-KO-05805) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000063084
NCBI RefSeq
NM_013842
Target Region
Exon 2
Size of Effective Region
~1.0 kb
Detailed Document
Overview of Gene Research
Xbp1, short for X-box binding protein 1, is a transcription factor. It is a key regulator in the unfolded protein response (UPR) pathway, which is activated when endoplasmic reticulum (ER) homeostasis is disrupted. Xbp1's dynamic form is controlled by alternative splicing in response to ER stress, and it is essential for cell fate determination under such stress [4]. Genetic models, like knockout (KO) and conditional knockout (CKO) mouse models, have been crucial in studying its functions.
In non-alcoholic steatohepatitis (NASH), Xbp1 expression was upregulated in patient liver samples. Hepatocyte-specific Xbp1 knockout (Xbp1ΔHep) and macrophage-specific Xbp1 knockout (Xbp1ΔMf) mice fed high-fat or methionine/choline-deficient diets showed inhibited steatohepatitis development compared to wild-type mice. Xbp1-deleted macrophages reduced steatohepatitis by decreasing NLRP3 expression and pro-inflammatory cytokine secretion, and also prevented hepatic stellate cell activation, leading to less fibrosis. Thus, Xbp1 is a potential target for NASH treatment [1]. In colorectal cancer, ablation of Xbp1 in tumor-associated macrophages (TAMs) inhibited the expression of pro-tumor cytokines and enhanced macrophage phagocytosis, suggesting Xbp1 activation in TAMs drives CRC progression and targeting it could be a therapeutic strategy [2]. In MYC-driven breast cancer, Xbp1 was found to be a synthetic lethal partner of MYC. Silencing Xbp1 selectively blocked the growth of MYC-hyperactivated cells, and pharmacological inhibition of IRE1 (which is related to Xbp1 in the UPR) restrained MYC-overexpressing tumor growth in preclinical models [3].
In conclusion, Xbp1 is a vital transcription factor in the UPR pathway, playing a significant role in cell fate determination during ER stress. Studies using KO and CKO mouse models have revealed its importance in diseases such as NASH, colorectal cancer, and MYC-driven breast cancer, highlighting its potential as a therapeutic target in these disease areas.
References:
1. Wang, Qi, Zhou, Haoming, Bu, Qingfa, Wang, Mingming, Lu, Ling. 2022. Role of XBP1 in regulating the progression of non-alcoholic steatohepatitis. In Journal of hepatology, 77, 312-325. doi:10.1016/j.jhep.2022.02.031. https://pubmed.ncbi.nlm.nih.gov/35292349/
2. Zhao, Yahui, Zhang, Weina, Huo, Miaomiao, Xu, Ningzhi, Zhu, Hongxia. 2021. XBP1 regulates the protumoral function of tumor-associated macrophages in human colorectal cancer. In Signal transduction and targeted therapy, 6, 357. doi:10.1038/s41392-021-00761-7. https://pubmed.ncbi.nlm.nih.gov/34667145/
3. Zhao, Na, Cao, Jin, Xu, Longyong, Lewis, Michael T, Chen, Xi. 2018. Pharmacological targeting of MYC-regulated IRE1/XBP1 pathway suppresses MYC-driven breast cancer. In The Journal of clinical investigation, 128, 1283-1299. doi:10.1172/JCI95873. https://pubmed.ncbi.nlm.nih.gov/29480818/
4. Chen, Shanshan, Chen, Jing, Hua, Xin, Sha, Jun, Zhu, Xiaoli. 2020. The emerging role of XBP1 in cancer. In Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 127, 110069. doi:10.1016/j.biopha.2020.110069. https://pubmed.ncbi.nlm.nih.gov/32294597/
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