C57BL/6JCya-Dusp6em1flox/Cya
Common Name:
Dusp6-flox
Product ID:
S-CKO-13779
Background:
C57BL/6JCya
Product Type
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Genotype
Sex
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Basic Information
Strain Name
Dusp6-flox
Strain ID
CKOCMP-67603-Dusp6-B6J-VA
Gene Name
Product ID
S-CKO-13779
Gene Alias
1300019I03Rik; MKP-3; MKP3; PYST1
Background
C57BL/6JCya
NCBI ID
Modification
Conditional knockout
Chromosome
10
Phenotype
Document
Application
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Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Dusp6em1flox/Cya mice (Catalog S-CKO-13779) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000020118
NCBI RefSeq
NM_026268
Target Region
Exon 1~2
Size of Effective Region
~2.0 kb
Detailed Document
Overview of Gene Research
Dusp6, also known as MKP3, is a dual-specificity phosphatase with a conserved function in the dephosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) [2]. It is involved in multiple signaling pathways, including the MAPK pathway, and plays a crucial role in various biological processes, such as cell proliferation, differentiation, and inflammation [1,2,4]. Genetic models, like knockout mouse models, have been instrumental in studying its functions.
In myeloproliferative neoplasms (MPNs) transforming to secondary acute myeloid leukemia (sAML), Dusp6 expression is aberrantly increased. Pharmacologic targeting of Dusp6 inhibits S6 and JAK-STAT signaling, reduces inflammatory cytokine production, and suppresses disease development in MPN mouse models and sAML patient-derived xenografts (PDXs) [1].
In the context of myocardial infarction, Dusp6 deficiency attenuates neutrophil-mediated cardiac damage in the acute inflammatory phase. Mechanistically, Dusp6 is transcriptionally activated by p38-C/EBPβ signaling and maintains p-p38 activity [2].
In HER2+ breast cancer, Dusp6 expression is induced during re-proliferation from dormant drug-tolerant cells. Its pharmacological blockade prevents therapy tolerance development under HER2 inhibitor therapy [3].
In MAPK pathway-driven cancers, dual inactivation of Dusp4 and Dusp6 impairs the growth of NRAS and BRAF mutant cells [4].
In colorectal cancer, Dusp6 can dephosphorylate Notch1, regulating its stability and transcriptional activity, and promoting cancer cell proliferation [5].
In colon cancer, PKN2 can inhibit M2 phenotype polarization of tumor-associated macrophages via regulating the Dusp6-Erk1/2 pathway [6].
Mutations in Dusp6 are identified in individuals with congenital hypogonadotropic hypogonadism [7].
Dusp6 deficiency attenuates neurodegeneration after global cerebral ischemia, as Dusp6 is induced in hippocampal CA1 neurons after ischemia, and its deficiency enhances Erk1/2 phosphorylation and nuclear translocation [8].
In Xenopus, Dusp6 is required for pre-placodal ectoderm formation by mediating FGF signaling [9].
In renal cell carcinoma, diminished Dusp6 expression is linked to disease progression, and calcium saccharate can enhance Dusp6 expression, inhibiting tumor cell proliferation and metabolic rewiring [10].
In conclusion, Dusp6 is a key regulator in multiple biological processes, mainly through its function in dephosphorylating ERK1/2. The use of Dusp6 knockout or conditional knockout mouse models has revealed its significance in diseases such as hematological malignancies, cardiovascular diseases, breast cancer, various cancers, neurodegenerative diseases, and developmental processes. Understanding Dusp6 provides potential therapeutic targets for these diseases.
References:
1. Kong, Tim, Laranjeira, Angelo B A, Yang, Kangning, Huang, Sidong, Oh, Stephen T. 2022. DUSP6 mediates resistance to JAK2 inhibition and drives leukemic progression. In Nature cancer, 4, 108-127. doi:10.1038/s43018-022-00486-8. https://pubmed.ncbi.nlm.nih.gov/36581736/
2. Zhou, Xiaohai, Zhang, Chenyang, Wu, Xueying, Zhu, Xiaojun, Xiong, Jing-Wei. 2022. Dusp6 deficiency attenuates neutrophil-mediated cardiac damage in the acute inflammatory phase of myocardial infarction. In Nature communications, 13, 6672. doi:10.1038/s41467-022-33631-z. https://pubmed.ncbi.nlm.nih.gov/36335128/
3. Momeny, Majid, Tienhaara, Mari, Sharma, Mukund, Kurppa, Kari J, Westermarck, Jukka. 2024. DUSP6 inhibition overcomes neuregulin/HER3-driven therapy tolerance in HER2+ breast cancer. In EMBO molecular medicine, 16, 1603-1629. doi:10.1038/s44321-024-00088-0. https://pubmed.ncbi.nlm.nih.gov/38886591/
4. Ito, Takahiro, Young, Michael J, Li, Ruitong, Zamanighomi, Mahdi, Sellers, William R. 2021. Paralog knockout profiling identifies DUSP4 and DUSP6 as a digenic dependence in MAPK pathway-driven cancers. In Nature genetics, 53, 1664-1672. doi:10.1038/s41588-021-00967-z. https://pubmed.ncbi.nlm.nih.gov/34857952/
5. Png, Chin Wen, Weerasooriya, Madhushanee, Li, Heng, Tan, Ker-Kan, Zhang, Yongliang. 2024. DUSP6 regulates Notch1 signalling in colorectal cancer. In Nature communications, 15, 10087. doi:10.1038/s41467-024-54383-y. https://pubmed.ncbi.nlm.nih.gov/39572549/
6. Cheng, Yang, Zhu, Yun, Xu, Jiajia, Geng, Lanlan, Gong, Sitang. 2018. PKN2 in colon cancer cells inhibits M2 phenotype polarization of tumor-associated macrophages via regulating DUSP6-Erk1/2 pathway. In Molecular cancer, 17, 13. doi:10.1186/s12943-017-0747-z. https://pubmed.ncbi.nlm.nih.gov/29368606/
7. Miraoui, Hichem, Dwyer, Andrew A, Sykiotis, Gerasimos P, Lage, Kasper, Pitteloud, Nelly. . Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism. In American journal of human genetics, 92, 725-43. doi:10.1016/j.ajhg.2013.04.008. https://pubmed.ncbi.nlm.nih.gov/23643382/
8. Weng, Yi-Chinn, Huang, Yu-Ting, Chiang, I-Chen, Tan, Tse-Hua, Chou, Wen-Hai. 2023. DUSP6 Deficiency Attenuates Neurodegeneration after Global Cerebral Ischemia. In International journal of molecular sciences, 24, . doi:10.3390/ijms24097690. https://pubmed.ncbi.nlm.nih.gov/37175394/
9. Tsukano, Kohei, Yamamoto, Takayoshi, Watanabe, Tomoko, Michiue, Tatsuo. 2022. Xenopus Dusp6 modulates FGF signaling to precisely pattern pre-placodal ectoderm. In Developmental biology, 488, 81-90. doi:10.1016/j.ydbio.2022.05.009. https://pubmed.ncbi.nlm.nih.gov/35598626/
10. Liu, Huan, Wang, Longsheng, Shi, Xiaokai, Chen, Yonghui, Zhang, Tao. 2024. Calcium saccharate/DUSP6 suppresses renal cell carcinoma glycolytic metabolism and boosts sunitinib efficacy via the ERK-AKT pathway. In Biochemical pharmacology, 224, 116247. doi:10.1016/j.bcp.2024.116247. https://pubmed.ncbi.nlm.nih.gov/38697311/
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