C57BL/6JCya-Kdm6aem1flox/Cya
Common Name:
Kdm6a-flox
Product ID:
S-CKO-06567
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
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Basic Information
Strain Name
Kdm6a-flox
Strain ID
CKOCMP-22289-Kdm6a-B6J-VB
Gene Name
Product ID
S-CKO-06567
Gene Alias
Utx
Background
C57BL/6JCya
NCBI ID
Modification
Conditional knockout
Chromosome
X
Phenotype
Document
Application
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Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Kdm6aem1flox/Cya mice (Catalog S-CKO-06567) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000052368
NCBI RefSeq
NM_009483
Target Region
Exon 3
Size of Effective Region
~1.5 kb
Detailed Document
Overview of Gene Research
Kdm6a, also known as UTX, belongs to the KDM6 family of histone H3 lysine 27 (H3K27) demethylases. It contains TPR and JmjC domains, and can catalyze the removal of di-and trimethylation on H3K27. Kdm6a physically associates with histone H3 lysine 4 monomethyltransferases MLL3 (KMT2C) and MLL4 (KMT2D), and is important for cell differentiation, development, and is implicated in various diseases [1].
In pancreatic ductal adenocarcinoma (PDAC), the genetically engineered, pancreas-specific Kdm6a knockout (KO) mouse model showed that Kdm6a loss correlates with increased tumor-associated neutrophils and neutrophil extracellular traps (NET) formation. Kdm6a-deficient PDAC cells secrete higher levels of CXCL1 protein, which recruits neutrophils. Treating with a CXCL1 neutralizing antibody in a syngeneic orthotopic mouse model suppressed tumor growth, suggesting the CXCL1-CXCR2 axis as a candidate target in PDAC with Kdm6a loss [2].
In small cell lung cancer (SCLC), a CRISPR-based autochthonous SCLC genetically engineered mouse model demonstrated that Kdm6a inactivation induced plasticity from ASCL1 to NEUROD1 subtype, by altering the chromatin state at enhancers of neuroendocrine genes [3].
In multiple myeloma (MM), disrupting Kdm6a in isogenic MM cells led to decreased expression of immune response genes like NLRC5 and CIITA, and reduced T-cell infiltration in K-RAS-transformed murine fibroblasts with Kdm6a loss [4].
In conclusion, Kdm6a plays crucial roles in development, differentiation, and disease through its histone demethylase activity. The use of KO and other genetic mouse models has revealed its impact on tumor immune microenvironment in PDAC, subtype plasticity in SCLC, and immune response gene regulation in MM, providing insights into disease mechanisms and potential therapeutic targets.
References:
1. Tran, Nhien, Broun, Aaron, Ge, Kai. 2020. Lysine Demethylase KDM6A in Differentiation, Development, and Cancer. In Molecular and cellular biology, 40, . doi:10.1128/MCB.00341-20. https://pubmed.ncbi.nlm.nih.gov/32817139/
2. Yang, Jing, Jin, Lin, Kim, Hong Sun, Crawford, Howard, Shi, Jiaqi. . KDM6A Loss Recruits Tumor-Associated Neutrophils and Promotes Neutrophil Extracellular Trap Formation in Pancreatic Cancer. In Cancer research, 82, 4247-4260. doi:10.1158/0008-5472.CAN-22-0968. https://pubmed.ncbi.nlm.nih.gov/36306422/
3. Duplaquet, Leslie, Li, Yixiang, Booker, Matthew A, Haffner, Michael C, Oser, Matthew G. 2023. KDM6A epigenetically regulates subtype plasticity in small cell lung cancer. In Nature cell biology, 25, 1346-1358. doi:10.1038/s41556-023-01210-z. https://pubmed.ncbi.nlm.nih.gov/37591951/
4. Dupéré-Richer, Daphné, Riva, Alberto, Barwick, Benjamin G, Bennett, Richard L, Licht, Jonathan D. . KDM6A regulates immune response genes in multiple myeloma. In Blood, 144, 1508-1520. doi:10.1182/blood.2024024518. https://pubmed.ncbi.nlm.nih.gov/39046770/
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