C57BL/6JCya-Msh2em1flox/Cya
Common Name:
Msh2-flox
Product ID:
S-CKO-03793
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
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Basic Information
Strain Name
Msh2-flox
Strain ID
CKOCMP-17685-Msh2-B6J-VA
Gene Name
Product ID
S-CKO-03793
Gene Alias
-
Background
C57BL/6JCya
NCBI ID
Modification
Conditional knockout
Chromosome
17
Phenotype
Document
Application
--
Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Msh2em1flox/Cya mice (Catalog S-CKO-03793) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000024967
NCBI RefSeq
NM_008628.3
Target Region
Exon 2~3
Size of Effective Region
~2.4 kb
Detailed Document
Overview of Gene Research
Msh2, short for MutS homolog 2, is an essential gene involved in DNA mismatch repair (MMR) pathway [1,3,4,5,6,7,8,9]. The proteins encoded by Msh2, as a part of complexes like MutSα (MSH2-MSH6) and MutSβ (MSH2-MSH3), are crucial for recognizing and repairing DNA mismatches, thus maintaining genome stability [7,9]. MMR deficiency can lead to cancer development and impacts cancer cell response to chemotherapy [7].
In Arabidopsis, Msh2 acts as a master regulator of meiotic DSB repair, stimulating interfering crossovers and inhibiting non-interfering crossovers in response to genetic polymorphism [2]. In Saccharomyces cerevisiae, the Msh2-Msh3 complex not only functions in post-replicative MMR but also contributes to genome stability through homologous recombination, double-strand break repair, and the DNA damage response, yet it can also promote genome instability through trinucleotide repeat expansions [3]. In human colorectal cancer cell lines, a methylation tolerance-based functional assay can assess the effects of variants of unknown significance (VUS) in Msh2 on DNA MMR, which may help in identifying patients with Lynch syndrome [1]. In bladder cancer, Msh2 is a mediator of cisplatin sensitivity, and circLIFR can synergize with Msh2 to positively modulate cisplatin-sensitivity through the MutSα/ATM-p73 axis [4]. Loss of Msh2 protein in primary prostate cancer is correlated with Msh2 inactivation, hypermutation, and higher tumor-infiltrating lymphocyte density, especially common in very high-grade primary tumors [8].
In conclusion, Msh2 is vital for DNA mismatch repair and genome stability. Its functions are revealed through studies in various organisms and cell lines. Defects in Msh2 are associated with multiple diseases, especially cancers like Lynch syndrome-associated endometrial cancer, bladder cancer, and prostate cancer. Understanding Msh2 helps in comprehending disease mechanisms and may potentially guide cancer treatment strategies.
References:
1. Bouvet, Delphine, Bodo, Sahra, Munier, Annie, Coulet, Florence, Muleris, Martine. 2019. Methylation Tolerance-Based Functional Assay to Assess Variants of Unknown Significance in the MLH1 and MSH2 Genes and Identify Patients With Lynch Syndrome. In Gastroenterology, 157, 421-431. doi:10.1053/j.gastro.2019.03.071. https://pubmed.ncbi.nlm.nih.gov/30998989/
2. Dluzewska, Julia, Dziegielewski, Wojciech, Szymanska-Lejman, Maja, Higgins, James D, Ziolkowski, Piotr A. 2023. MSH2 stimulates interfering and inhibits non-interfering crossovers in response to genetic polymorphism. In Nature communications, 14, 6716. doi:10.1038/s41467-023-42511-z. https://pubmed.ncbi.nlm.nih.gov/37872134/
3. Medina-Rivera, Melisa, Phelps, Samantha, Sridharan, Madhumita, Balakrishnan, Lata, Surtees, Jennifer A. . Elevated MSH2 MSH3 expression interferes with DNA metabolism in vivo. In Nucleic acids research, 51, 12185-12206. doi:10.1093/nar/gkad934. https://pubmed.ncbi.nlm.nih.gov/37930834/
4. Zhang, Hui, Xiao, Xingyuan, Wei, Wenjie, Jiang, Guosong, Zhang, Xiaoping. 2021. CircLIFR synergizes with MSH2 to attenuate chemoresistance via MutSα/ATM-p73 axis in bladder cancer. In Molecular cancer, 20, 70. doi:10.1186/s12943-021-01360-4. https://pubmed.ncbi.nlm.nih.gov/33874956/
5. Huang, Rong, Deng, Xiangyu, Zhang, Zhenhua, Wen, Qinglian, Li, Dan. 2022. Lynch Syndrome-Associated Endometrial Cancer With Combined EPCAM-MSH2 Deletion: A Case Report. In Frontiers in oncology, 12, 856452. doi:10.3389/fonc.2022.856452. https://pubmed.ncbi.nlm.nih.gov/35311082/
6. DuPrie, Matthew L, Palacio, Tatiana, Calil, Felipe A, Kolodner, Richard D, Putnam, Christopher D. 2022. Mlh1 interacts with both Msh2 and Msh6 for recruitment during mismatch repair. In DNA repair, 119, 103405. doi:10.1016/j.dnarep.2022.103405. https://pubmed.ncbi.nlm.nih.gov/36122480/
7. Wu, Qiong, Huang, Yaping, Gu, Liya, Chang, Zhijie, Li, Guo-Min. 2021. OTUB1 stabilizes mismatch repair protein MSH2 by blocking ubiquitination. In The Journal of biological chemistry, 296, 100466. doi:10.1016/j.jbc.2021.100466. https://pubmed.ncbi.nlm.nih.gov/33640455/
8. Guedes, Liana B, Antonarakis, Emmanuel S, Schweizer, Michael T, Pritchard, Colin C, Lotan, Tamara L. 2017. MSH2 Loss in Primary Prostate Cancer. In Clinical cancer research : an official journal of the American Association for Cancer Research, 23, 6863-6874. doi:10.1158/1078-0432.CCR-17-0955. https://pubmed.ncbi.nlm.nih.gov/28790115/
9. Thirumal Kumar, D, Susmita, B, Judith, E, George Priya Doss, C, Zayed, Hatem. 2019. Elucidating the role of interacting residues of the MSH2-MSH6 complex in DNA repair mechanism: A computational approach. In Advances in protein chemistry and structural biology, 115, 325-350. doi:10.1016/bs.apcsb.2018.11.005. https://pubmed.ncbi.nlm.nih.gov/30798936/
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