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C57BL/6JCya-Sf3b1em1/Cya
Common Name:
Sf3b1-KO
Product ID:
S-KO-17122
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
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Price:
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Basic Information
Strain Name
Sf3b1-KO
Strain ID
KOCMP-81898-Sf3b1-B6J-VA
Gene Name
Sf3b1
Product ID
S-KO-17122
Gene Alias
155kDa; 2810001M05Rik; Prp10; SAP155; SF3b155; TA-8; Targ4
Background
C57BL/6JCya
NCBI ID
81898
Modification
Conventional knockout
Chromosome
1
Phenotype
MGI:1932339
Document
Click here to download >>
Application
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Rare Disease Data Center >>
Note
Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Sf3b1em1/Cya mice (Catalog S-KO-17122) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000027127
NCBI RefSeq
NM_031179
Target Region
Exon 7
Size of Effective Region
~0.2 kb
Detailed Document
Click here to download >>
Overview of Gene Research
SF3B1 encodes the largest subunit of the splicing factor 3b protein complex, which is crucial for spliceosome assembly and mRNA splicing. The normal function of SF3B1 is essential for proper pre-mRNA splicing, and any aberration in this process can impact numerous cellular processes and gene expressions [1].

Mutations in SF3B1 are common in hematological malignancies, especially in myelodysplastic syndromes (MDS). SF3B1 -mutant MDS is often associated with the presence of ring sideroblasts in the bone marrow, ineffective erythropoiesis, and an indolent clinical course. These mutations cause aberrant pre-mRNA splicing of many target genes, affecting hematopoiesis. Some downstream effects converge on common cellular processes like hyperactivation of NF -κB signaling and increased R -loops [2,3]. In SF3B1 -mutant MDS, mis -splicing of coenzyme A synthase (COASY) affects heme biosynthesis and erythropoiesis. Supplementation with COASY substrate (vitamin B5) can rescue erythropoiesis differentiation defects in MDS-RS primary patient cells [5]. Also, in SF3B1 -mutant cells, the defective response to PARP -induced replication stress occurs via down -regulation of CINP, leading to increased replication fork origin firing and loss of phosphorylated CHK1 induction [4]. Silencing of GPATCH8, a trans factor required for mutant SF3B1 -induced splicing alterations, can correct one -third of mutant SF3B1 -dependent splicing defects and improve dysfunctional hematopoiesis in SF3B1 -mutant mice [6].

In conclusion, SF3B1 is vital for mRNA splicing. Its mutations in hematological malignancies, particularly MDS, lead to aberrant splicing, influencing various cellular processes. The study of SF3B1 -mutant models, such as mice, has provided insights into the role of SF3B1 in hematopoiesis, erythropoiesis, and DNA replication stress response, which may help develop targeted therapies for related diseases.

References:

1. Cilloni, Daniela, Itri, Federico, Bonuomo, Valentina, Petiti, Jessica. 2022. SF3B1 Mutations in Hematological Malignancies. In Cancers, 14, . doi:10.3390/cancers14194927. https://pubmed.ncbi.nlm.nih.gov/36230848/

2. Pellagatti, Andrea, Boultwood, Jacqueline. 2020. SF3B1 mutant myelodysplastic syndrome: Recent advances. In Advances in biological regulation, 79, 100776. doi:10.1016/j.jbior.2020.100776. https://pubmed.ncbi.nlm.nih.gov/33358369/

3. Malcovati, Luca, Stevenson, Kristen, Papaemmanuil, Elli, Hellstrom-Lindberg, Eva, Cazzola, Mario. . SF3B1-mutant MDS as a distinct disease subtype: a proposal from the International Working Group for the Prognosis of MDS. In Blood, 136, 157-170. doi:10.1182/blood.2020004850. https://pubmed.ncbi.nlm.nih.gov/32347921/

4. Bland, Philip, Saville, Harry, Wai, Patty T, Lord, Christopher J, Natrajan, Rachael. 2023. SF3B1 hotspot mutations confer sensitivity to PARP inhibition by eliciting a defective replication stress response. In Nature genetics, 55, 1311-1323. doi:10.1038/s41588-023-01460-5. https://pubmed.ncbi.nlm.nih.gov/37524790/

5. Mian, Syed A, Philippe, Céline, Maniati, Eleni, Gribben, John G, Rouault-Pierre, Kevin. 2023. Vitamin B5 and succinyl-CoA improve ineffective erythropoiesis in SF3B1-mutated myelodysplasia. In Science translational medicine, 15, eabn5135. doi:10.1126/scitranslmed.abn5135. https://pubmed.ncbi.nlm.nih.gov/36857430/

6. Benbarche, Salima, Pineda, Jose Mario Bello, Galvis, Laura Baquero, Bradley, Robert K, Abdel-Wahab, Omar. 2024. GPATCH8 modulates mutant SF3B1 mis-splicing and pathogenicity in hematologic malignancies. In Molecular cell, 84, 1886-1903.e10. doi:10.1016/j.molcel.2024.04.006. https://pubmed.ncbi.nlm.nih.gov/38688280/

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
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