C57BL/6JCya-Dis3l2em1flox/Cya
Common Name:
Dis3l2-flox
Product ID:
S-CKO-05371
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
Quantity
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Basic Information
Strain Name
Dis3l2-flox
Strain ID
CKOCMP-208718-Dis3l2-B6J-VA
Gene Name
Product ID
S-CKO-05371
Gene Alias
4930429A22Rik; 8030493P09Rik
Background
C57BL/6JCya
NCBI ID
Modification
Conditional knockout
Chromosome
1
Phenotype
Document
Application
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Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Dis3l2em1flox/Cya mice (Catalog S-CKO-05371) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000168237
NCBI RefSeq
NM_001172157
Target Region
Exon 8
Size of Effective Region
~1.1 kb
Detailed Document
Overview of Gene Research
DIS3L2 is an RNA-binding protein with 3'-5' exoribonuclease activity. It contains RNA-binding domains (two CSD domains and one S1 domain) and an RNB domain for exoribonuclease activity. DIS3L2 is predominantly in the cytoplasm, where it recognizes and degrades uridylated cytoplasmic RNAs like pre-microRNA, mature microRNA, mRNA, and non-coding RNAs, playing a key role in cytoplasmic RNA surveillance and decay. It is involved in multiple biological processes such as cell division, proliferation, differentiation, and apoptosis [1]. Mutations in DIS3L2 have been linked to Perlman syndrome [1,7].
Conditional ablation of Dis3l2 in pre-meiotic germ cells of male mice using Stra8-Cre mice leads to impaired spermatogonial differentiation, hindered spermatocyte meiotic progression, and cell apoptosis, resulting in defective spermatogenesis and male infertility. This indicates the crucial role of DIS3L2-mediated RNA degradation in maintaining the correct transcriptome during spermatogenesis [2].
In female mice, oocyte-specific Dis3l2 knockout (Dis3l2cKO) causes almost all oocytes to arrest at the germinal vesicle stage, and female mice are infertile, as uridylated-poly(A) RNAs accumulate due to insufficient degradation by DIS3L2 [3].
In Drosophila, a dis3L2 null mutant shows that the catalytic activity of Dis3L2 is required to control cell proliferation, and in human kidney HEK-293T cells, loss of DIS3L2 also results in cell proliferation, with an increase in the PI3-Kinase/AKT signalling pathway [4].
In colorectal cancer cells, knockdown of DIS3L2 reduces the viability of highly oncogenic cells and disturbs metastasis-associated properties, and downregulates the mTOR signalling pathway [5].
In hepatocellular carcinoma, DIS3L2 promotes cancer progression via hnRNP U-mediated alternative splicing, generating an oncogenic splicing variant, Rac1b [6].
In conclusion, DIS3L2 is essential for cytoplasmic RNA surveillance and decay, and is involved in various biological processes. Through gene knockout and conditional knockout mouse models, as well as other model-based research, its roles in spermatogenesis, oocyte maturation, cell proliferation, and cancer development have been revealed. The study of DIS3L2 provides insights into RNA metabolism and the mechanisms underlying diseases such as Perlman syndrome and various cancers.
References:
1. Luan, Siyu, Luo, Junyun, Liu, Hui, Li, Zhaoyong. 2019. Regulation of RNA decay and cellular function by 3'-5' exoribonuclease DIS3L2. In RNA biology, 16, 160-165. doi:10.1080/15476286.2018.1564466. https://pubmed.ncbi.nlm.nih.gov/30638126/
2. Li, Nana, Yu, Junjie, Feng, Yan-Qin, Xu, Yu, Wang, Zhengpin. 2024. Conditional ablation of DIS3L2 ribonuclease in pre-meiotic germ cells causes defective spermatogenesis and infertility in male mice. In Theranostics, 14, 5621-5642. doi:10.7150/thno.98620. https://pubmed.ncbi.nlm.nih.gov/39310107/
3. Wu, Di, Pedroza, Monique, Chang, Jonathan, Dean, Jurrien. . DIS3L2 ribonuclease degrades terminal-uridylated RNA to ensure oocyte maturation and female fertility. In Nucleic acids research, 51, 3078-3093. doi:10.1093/nar/gkad061. https://pubmed.ncbi.nlm.nih.gov/36727488/
4. Towler, Benjamin P, Pashler, Amy L, Haime, Hope J, Arraiano, Cecilia M, Newbury, Sarah F. 2020. Dis3L2 regulates cell proliferation and tissue growth through a conserved mechanism. In PLoS genetics, 16, e1009297. doi:10.1371/journal.pgen.1009297. https://pubmed.ncbi.nlm.nih.gov/33370287/
5. García-Moreno, Juan F, Lacerda, Rafaela, da Costa, Paulo J, Matos, Paulo, Romão, Luísa. 2023. DIS3L2 knockdown impairs key oncogenic properties of colorectal cancer cells via the mTOR signaling pathway. In Cellular and molecular life sciences : CMLS, 80, 185. doi:10.1007/s00018-023-04833-5. https://pubmed.ncbi.nlm.nih.gov/37340282/
6. Xing, Songge, Li, Zhaoyong, Ma, Wenhao, Jia, Wei-Dong, Zhang, Huafeng. 2019. DIS3L2 Promotes Progression of Hepatocellular Carcinoma via hnRNP U-Mediated Alternative Splicing. In Cancer research, 79, 4923-4936. doi:10.1158/0008-5472.CAN-19-0376. https://pubmed.ncbi.nlm.nih.gov/31331910/
7. Al Ghadeer, Hussain A, Alghazal, Fouad A, Alessa, Marwah A, Almumtin, Khulud A, Abu Sinah, Ahmed K. 2023. DIS3L2 Gene Mutation Causes the Perlman Syndrome of Overgrowth and Wilms Tumor Susceptibility. In Cureus, 15, e49777. doi:10.7759/cureus.49777. https://pubmed.ncbi.nlm.nih.gov/38161545/
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