C57BL/6JCya-Waplem1flox/Cya
Common Name:
Wapl-flox
Product ID:
S-CKO-06333
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
Quantity
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Basic Information
Strain Name
Wapl-flox
Strain ID
CKOCMP-218914-Wapl-B6J-VA
Gene Name
Product ID
S-CKO-06333
Gene Alias
A530089A20Rik; DIF-2; FOE; Wapal
Background
C57BL/6JCya
NCBI ID
Modification
Conditional knockout
Chromosome
14
Phenotype
Document
Application
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Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Waplem1flox/Cya mice (Catalog S-CKO-06333) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000048263
NCBI RefSeq
NM_001004436
Target Region
Exon 3~4
Size of Effective Region
~4.3 kb
Detailed Document
Overview of Gene Research
Wapl, short for wings apart-like protein homolog, is a crucial factor associated with the Cohesin complex. The Cohesin complex, consisting of core subunits Smc1, Smc3, Scc1, and SA2 (or SA1), topologically entraps sister DNA molecules for sister chromatid cohesion in S-phase. Wapl's key function is to bind the Cohesin complex, inducing its disassociation from mitotic chromosomes to enable proper sister chromatid resolution and separation, ensuring accurate chromosome segregation [1]. It also plays roles in regulating 3D genome folding, enhancer-promoter interactions, and gene expression, and is involved in processes like neural wiring and oocyte meiotic progression [2,3,4,7].
In Nipbl+/- mouse models, which mimic Cornelia de Lange syndrome due to NIPBL haploinsufficiency, decreasing Wapl dosage was found to partially correct embryonic growth and brain transcriptome phenotypes. This suggests that Wapl mutations might also contribute to human diseases, as the patterns of gene dysregulation in WaplΔ/+ embryonic mouse brain were highly similar to those in Nipbl heterozygotes [6]. In WAPL overexpressing mice (WAPL Tg mice), CIN lesions developed without HPV E6/E7, indicating WAPL's role in cervical cancer development by increasing estrogen receptor 1 (ESR1) sensitivity through activating MACROD1, leading to the expression of MYC and Cyclin D1 [5]. In porcine and mouse oocytes, WAPL depletion led to accelerated meiotic progression, compromised spindle assembly and chromosome alignment, highlighting its role in oocyte meiotic progression through maintaining BUB3 protein levels and spindle assembly checkpoint (SAC) activity [7].
In conclusion, Wapl is essential for accurate chromosome segregation, 3D genome organization, gene expression regulation, and normal development. Mouse models, such as WAPL Tg mice, Nipbl+/- mice with Wapl dosage reduction, and WAPL-depleted oocyte models, have been instrumental in uncovering Wapl's role in diseases like cervical cancer and potential contributions to human syndromes, as well as its function in oocyte meiosis. These studies provide insights into the molecular mechanisms underlying these biological processes and disease conditions.
References:
1. Yuan, Xueying, Yan, Lu, Chen, Qinfu, Yan, Haiyan, Wang, Fangwei. 2024. Molecular mechanism and functional significance of Wapl interaction with the Cohesin complex. In Proceedings of the National Academy of Sciences of the United States of America, 121, e2405177121. doi:10.1073/pnas.2405177121. https://pubmed.ncbi.nlm.nih.gov/39110738/
2. Hsieh, Tsung-Han S, Cattoglio, Claudia, Slobodyanyuk, Elena, Darzacq, Xavier, Tjian, Robert. 2022. Enhancer-promoter interactions and transcription are largely maintained upon acute loss of CTCF, cohesin, WAPL or YY1. In Nature genetics, 54, 1919-1932. doi:10.1038/s41588-022-01223-8. https://pubmed.ncbi.nlm.nih.gov/36471071/
3. Wutz, Gordana, Várnai, Csilla, Nagasaka, Kota, Fraser, Peter, Peters, Jan-Michael. 2017. Topologically associating domains and chromatin loops depend on cohesin and are regulated by CTCF, WAPL, and PDS5 proteins. In The EMBO journal, 36, 3573-3599. doi:10.15252/embj.201798004. https://pubmed.ncbi.nlm.nih.gov/29217591/
4. Kiefer, Lea, Chiosso, Anna, Langen, Jennifer, Mui, Michael H, Canzio, Daniele. 2023. WAPL functions as a rheostat of Protocadherin isoform diversity that controls neural wiring. In Science (New York, N.Y.), 380, eadf8440. doi:10.1126/science.adf8440. https://pubmed.ncbi.nlm.nih.gov/37347873/
5. Kumagai, Katsuyoshi, Takanashi, Masakatsu, Ohno, Shin-Ichiro, Oikawa, Kosuke, Kuroda, Masahiko. 2021. WAPL induces cervical intraepithelial neoplasia modulated with estrogen signaling without HPV E6/E7. In Oncogene, 40, 3695-3706. doi:10.1038/s41388-021-01787-5. https://pubmed.ncbi.nlm.nih.gov/33947962/
6. Kean, Connor M, Tracy, Christopher J, Mitra, Apratim, Kassis, Judith A, Pfeifer, Karl. 2022. Decreasing Wapl dosage partially corrects embryonic growth and brain transcriptome phenotypes in Nipbl+/- embryos. In Science advances, 8, eadd4136. doi:10.1126/sciadv.add4136. https://pubmed.ncbi.nlm.nih.gov/36449618/
7. Zhou, Changyin, Miao, Yilong, Zhang, Xue, Xiong, Bo. 2021. WAPL orchestrates porcine oocyte meiotic progression via control of spindle assembly checkpoint activity. In Reproductive biology and endocrinology : RB&E, 19, 57. doi:10.1186/s12958-021-00740-1. https://pubmed.ncbi.nlm.nih.gov/33874950/
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