C57BL/6JCya-Mlh1em1flox/Cya
Common Name:
Mlh1-flox
Product ID:
S-CKO-03741
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
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Basic Information
Strain Name
Mlh1-flox
Strain ID
CKOCMP-17350-Mlh1-B6J-VA
Gene Name
Product ID
S-CKO-03741
Gene Alias
1110035C23Rik
Background
C57BL/6JCya
NCBI ID
Modification
Conditional knockout
Chromosome
9
Phenotype
Document
Application
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Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Mlh1em1flox/Cya mice (Catalog S-CKO-03741) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000035079
NCBI RefSeq
NM_026810
Target Region
Exon 4
Size of Effective Region
~1.1 kb
Detailed Document
Overview of Gene Research
MLH1, Mut L homolog-1, is a key DNA mismatch repair protein [4]. It participates in maintaining genome stability by rectifying errors during DNA replication, thus playing a crucial role in preventing cancer development. The ubiquitin-proteasome system is involved in regulating MLH1 protein degradation, with the E3 ubiquitin ligase UBR4 and deubiquitylase USP5 oppositely modulating its stability [6].
MLH1 deficiency is associated with various cancers. In Lynch syndrome, a rare mechanism can be a germline monoallelic constitutional epimutation of the MLH1 promoter, which can lead to multiple malignancies like colorectal, vulvar, and endometrial cancers [1]. In colorectal cancer, MLH1 proficient cells are less sensitive to 5-Fluorouracil-induced cytotoxic effect, as MLH1 mediates cytoprotective nucleophagy by interacting with the autophagy marker LC3 [2]. Also, MLH1 promoter methylation can be a "second hit" in Lynch syndrome carcinogenesis, and a polymorphism (rs1800734) in its core promoter region is associated with an increased risk of colorectal cancer in the lower northeastern region of Thailand [3,5].
In conclusion, MLH1 is essential for DNA mismatch repair and genome maintenance. Its deficiency is linked to cancer development, especially in Lynch syndrome and colorectal cancer. Studies on MLH1-related mechanisms, such as its role in drug-induced cell death and promoter methylation, contribute to understanding cancer carcinogenesis and may provide potential targets for cancer prevention and treatment.
References:
1. Zyla, Roman, Graham, Tracy, Aronson, Melyssa, Mrkonjic, Miralem, Turashvili, Gulisa. 2021. MLH1 epimutation is a rare mechanism for Lynch syndrome: A case report and review of the literature. In Genes, chromosomes & cancer, 60, 635-639. doi:10.1002/gcc.22957. https://pubmed.ncbi.nlm.nih.gov/33934415/
2. Manzoor, Shaista, Saber-Ayad, Maha, Maghazachi, Azzam A, Hamid, Qutayba, Muhammad, Jibran Sualeh. 2021. MLH1 mediates cytoprotective nucleophagy to resist 5-Fluorouracil-induced cell death in colorectal carcinoma. In Neoplasia (New York, N.Y.), 24, 76-85. doi:10.1016/j.neo.2021.12.003. https://pubmed.ncbi.nlm.nih.gov/34952246/
3. Carnevali, Ileana Wanda, Cini, Giulia, Libera, Laura, Sessa, Fausto, Tibiletti, Maria Grazia. 2023. MLH1 Promoter Methylation Could Be the Second Hit in Lynch Syndrome Carcinogenesis. In Genes, 14, . doi:10.3390/genes14112060. https://pubmed.ncbi.nlm.nih.gov/38003003/
4. Huang, Yuling, Feng, Liu, Bao, Yongqiang, Li, Jingao, Jiang, Chunling. 2021. Expressing MLH1 in HCT116 cells increases cellular resistance to radiation by activating the PRKAC. In Experimental biology and medicine (Maywood, N.J.), 247, 426-432. doi:10.1177/15353702211059829. https://pubmed.ncbi.nlm.nih.gov/34787019/
5. Pongsavee, Malinee, Wisuwan, Kamol, Pongsavee, Kritpipat. 2023. MLH1 rs1800734 Pathogenic Variant among Patients with Colorectal Cancer in the Lower Northeastern Region of Thailand. In Asian Pacific journal of cancer prevention : APJCP, 24, 2911-2916. doi:10.31557/APJCP.2023.24.8.2911. https://pubmed.ncbi.nlm.nih.gov/37642081/
6. Mao, Chenyu, Li, Siqi, Che, Jun, Mao, Xinliang, Rao, Hai. 2024. The ubiquitin ligase UBR4 and the deubiquitylase USP5 modulate the stability of DNA mismatch repair protein MLH1. In The Journal of biological chemistry, 300, 107592. doi:10.1016/j.jbc.2024.107592. https://pubmed.ncbi.nlm.nih.gov/39032648/
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