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C57BL/6JCya-Smad4em1/Cya
Common Name:
Smad4-KO
Product ID:
S-KO-03093
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
Quantity
Price:
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Basic Information
Strain Name
Smad4-KO
Strain ID
KOCMP-17128-Smad4-B6J-VA
Gene Name
Smad4
Product ID
S-KO-03093
Gene Alias
D18Wsu70e; DPC4; Madh4
Background
C57BL/6JCya
NCBI ID
17128
Modification
Conventional knockout
Chromosome
18
Phenotype
MGI:894293
Document
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Application
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Rare Disease Data Center >>
Note
Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Smad4em1/Cya mice (Catalog S-KO-03093) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000025393
NCBI RefSeq
NM_008540
Target Region
Exon 3~4
Size of Effective Region
~1.6 kb
Detailed Document
Click here to download >>
Overview of Gene Research
Smad4, also known as DPC4, is a key signal transduction protein belonging to the Smads family. It is phosphorylated and activated by transmembrane serine-threonine receptor kinases in response to transforming growth factor beta (TGF-β) signaling via multiple pathways. As a tumor suppressor gene, it plays a crucial role in mediating cell functions like proliferation and apoptosis, and its inactivation is significantly associated with cancer development [1,2]. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, are valuable tools for studying its functions.

In pancreatic cancer, SMAD4 is specifically inactivated in about half of advanced cases, and its loss almost determines the orientation of TGF-β1-induced epithelial-mesenchymal transition (EMT) via the SMAD4-dependent canonical pathway, which also alters ferroptosis vulnerability [2,3]. In colorectal cancer (CRC), loss of SMAD4 expression is related to metastatic development and worse chemotherapy response. Moreover, SMAD4 mutations in patients with colorectal liver metastases are associated with a high likelihood of carrying RAS mutations, predicting worse overall survival. In an autochthonous mouse model, Smad4 loss and p53 loss synergize in intestinal carcinogenesis by downregulating p21 and activating the Wnt/β-catenin pathway [4,5]. In cholangiocarcinoma, SMAD4 downregulation affects the expression of STING1, and low SMAD4 and STING1 expression indicate poor prognosis [6]. A heterozygous variation in the SMAD4 gene in a four-generation family was found to co-segregate with autosomal-dominant congenital heart disease, and the mutant SMAD4 lost transactivation of key downstream target genes related to heart development [7].

In summary, Smad4 is essential in mediating TGF-β signaling and has a significant impact on cancer development, especially in pancreatic, colorectal, and cholangiocarcinoma. The study of Smad4 KO/CKO mouse models has provided insights into its role in carcinogenesis, EMT, and ferroptosis in cancer, as well as its association with congenital heart disease, contributing to our understanding of the molecular mechanisms underlying these diseases.

References:

1. McCarthy, Aoife J, Chetty, Runjan. 2018. Smad4/DPC4. In Journal of clinical pathology, 71, 661-664. doi:10.1136/jclinpath-2018-205095. https://pubmed.ncbi.nlm.nih.gov/29720405/

2. Xia, Xiang, Wu, Weidong, Huang, Chen, Huang, Kejian, Qiu, Zhengjun. 2014. SMAD4 and its role in pancreatic cancer. In Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 36, 111-9. doi:10.1007/s13277-014-2883-z. https://pubmed.ncbi.nlm.nih.gov/25464861/

3. Chen, Hai-di, Ye, Zeng, Hu, Hai-Feng, Yu, Xian-Jun, Qin, Yi. 2023. SMAD4 endows TGF-β1-induced highly invasive tumor cells with ferroptosis vulnerability in pancreatic cancer. In Acta pharmacologica Sinica, 45, 844-856. doi:10.1038/s41401-023-01199-z. https://pubmed.ncbi.nlm.nih.gov/38057506/

4. Xourafas, Dimitrios, Mizuno, Takashi, Cloyd, Jordan M. 2019. The impact of somatic SMAD4 mutations in colorectal liver metastases. In Chinese clinical oncology, 8, 52. doi:10.21037/cco.2019.08.04. https://pubmed.ncbi.nlm.nih.gov/31500428/

5. Park, Jun Won, Seo, Min-Jung, Cho, Kye Soo, Cheon, Jae Hee, Kim, Hark Kyun. 2022. Smad4 and p53 synergize in suppressing autochthonous intestinal cancer. In Cancer medicine, 11, 1925-1936. doi:10.1002/cam4.4533. https://pubmed.ncbi.nlm.nih.gov/35274815/

6. Shi, An-da, Zhao, Li-Ming, Sheng, Guo-Li, Li, Kang-Shuai, Zhang, Zong-Li. 2023. SMAD4 regulates the progression of cholangiocarcinoma by modulating the expression of STING1. In Journal of cellular and molecular medicine, 27, 2547-2561. doi:10.1111/jcmm.17857. https://pubmed.ncbi.nlm.nih.gov/37488750/

7. Wang, Yin, Xu, Ying-Jia, Yang, Chen-Xi, Yuan, Fang, Yang, Yi-Qing. 2022. SMAD4 loss-of-function mutation predisposes to congenital heart disease. In European journal of medical genetics, 66, 104677. doi:10.1016/j.ejmg.2022.104677. https://pubmed.ncbi.nlm.nih.gov/36496093/

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
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