C57BL/6JCya-Mdm4em1flox/Cya
Common Name:
Mdm4-flox
Product ID:
S-CKO-03695
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
Quantity
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Basic Information
Strain Name
Mdm4-flox
Strain ID
CKOCMP-17248-Mdm4-B6J-VA
Gene Name
Product ID
S-CKO-03695
Gene Alias
4933417N07Rik; Mdmx
Background
C57BL/6JCya
NCBI ID
Modification
Conditional knockout
Chromosome
1
Phenotype
Document
Application
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Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Mdm4em1flox/Cya mice (Catalog S-CKO-03695) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000067429
NCBI RefSeq
NM_008575
Target Region
Exon 5
Size of Effective Region
~0.9 kb
Detailed Document
Overview of Gene Research
Mdm4, also known as MDMX or HDMX (human MDMX), is a crucial negative regulator of the tumor suppressor p53 [6,7,8]. It is involved in cell proliferation, DNA repair, and apoptosis regulation, and its normal function is essential for maintaining proper cell function and response to stress [1,7]. Through its N-terminus transactivation domain engaging p53 and C-terminus RING domain binding to MDM2, Mdm4 restricts p53 transcriptional activity and, at least in development, aids MDM2's E3 ligase activity toward p53 [7].
MDM4 overexpression and amplification are linked to cancer formation, metastasis, and poor disease prognosis [1]. It is frequently amplified and upregulated in human cancers, blocking the expression of downstream target genes of the p53 pathway, contributing to overgrowth and apoptosis inhibition [3]. Some MDM4 SNPs in non-coding regions can affect its regulation by disrupting microRNA binding sites in 3'UTR, but studies on the association between its SNPs and cancer risk in different populations have led to conflicting conclusions [1]. MDM4 generates two mutually exclusive isoforms via alternative splicing: MDM4-FL encoding the full-length protein and MDM4-S, with previous results suggesting MDM4-S could be a tumor driver, though recent data indicate it may be a passenger isoform during tumorigenesis [2]. In p53 mutant colon cancer, MDM4 inhibits ferroptosis by regulating TRIM21/GPX4 expression, promoting cancer progression [4]. Pharmacological inhibition of MDM4 alleviates pulmonary fibrosis [5].
In conclusion, Mdm4 is a key negative regulator of p53, playing a significant role in cancer and pulmonary fibrosis. Its overexpression and genetic variations are associated with disease development. Research on Mdm4, especially through in vivo studies like potential KO/CKO mouse models (not directly mentioned in provided refs but relevant in general functional studies), helps understand its functions in disease-related biological processes, offering potential therapeutic strategies for cancer and pulmonary fibrosis [1,3,4,5].
References：
1. Almeida, Gabriela Mattevi, Castilho, Ana Clara, Adamoski, Douglas, Braun-Prado, Karin. 2022. MDM4: What do we know about the association between its polymorphisms and cancer? In Medical oncology (Northwood, London, England), 40, 61. doi:10.1007/s12032-022-01929-z. https://pubmed.ncbi.nlm.nih.gov/36566308/
2. Bardot, Boris, Toledo, Franck. 2017. Targeting MDM4 Splicing in Cancers. In Genes, 8, . doi:10.3390/genes8020082. https://pubmed.ncbi.nlm.nih.gov/28230750/
3. Wu, Jin, Lu, Guanting, Wang, Xinjiang. 2021. MDM4 alternative splicing and implication in MDM4 targeted cancer therapies. In American journal of cancer research, 11, 5864-5880. doi:. https://pubmed.ncbi.nlm.nih.gov/35018230/
4. Liu, Jie, Wei, Xujin, Xie, Yixuan, Zheng, Xiaoling, Huang, Qingling. 2024. MDM4 inhibits ferroptosis in p53 mutant colon cancer via regulating TRIM21/GPX4 expression. In Cell death & disease, 15, 825. doi:10.1038/s41419-024-07227-y. https://pubmed.ncbi.nlm.nih.gov/39543140/
5. Mei, Qianru, Yang, Zhenhua, Xiang, Zhengkai, Zhou, Yong, Qu, Jing. 2023. Pharmacological inhibition of MDM4 alleviates pulmonary fibrosis. In Theranostics, 13, 2787-2799. doi:10.7150/thno.81993. https://pubmed.ncbi.nlm.nih.gov/37284444/
6. Markey, Michael P. 2011. Regulation of MDM4. In Frontiers in bioscience (Landmark edition), 16, 1144-56. doi:. https://pubmed.ncbi.nlm.nih.gov/21196223/
7. Haupt, Sue, Mejía-Hernández, Javier Octavio, Vijayakumaran, Reshma, Keam, Simon P, Haupt, Ygal. . The long and the short of it: the MDM4 tail so far. In Journal of molecular cell biology, 11, 231-244. doi:10.1093/jmcb/mjz007. https://pubmed.ncbi.nlm.nih.gov/30689920/
8. Mancini, F, Di Conza, G, Monti, O, Pontecorvi, A, Moretti, F. 2010. Puzzling over MDM4-p53 network. In The international journal of biochemistry & cell biology, 42, 1080-3. doi:10.1016/j.biocel.2010.04.010. https://pubmed.ncbi.nlm.nih.gov/20417304/
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