C57BL/6JCya-Spred1em1/Cya
Common Name:
Spred1-KO
Product ID:
S-KO-00890
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
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Basic Information
Strain Name
Spred1-KO
Strain ID
KOCMP-114715-Spred1-B6J-VA
Gene Name
Product ID
S-KO-00890
Gene Alias
5730461F13Rik
Background
C57BL/6JCya
NCBI ID
Modification
Conventional knockout
Chromosome
2
Phenotype
Document
Application
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Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Spred1em1/Cya mice (Catalog S-KO-00890) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000028829
NCBI RefSeq
NM_033524
Target Region
Exon 2
Size of Effective Region
~1.2 kb
Detailed Document
Overview of Gene Research
Spred1, or Sprouty-related, EVH1 domain-containing protein 1, is a negative regulator of the RAS-MAPK signaling pathway. This pathway is crucial for cellular growth, development, and differentiation [5,6,7]. Genetic models, such as gene knockout (KO) mouse models, have been valuable in studying Spred1's function.
In CML, Spred1 knockout in SCLtTA/BCR-ABL CML mice (globally, or restricted to hematopoietic or endothelial cells) led to the transformation of chronic phase CML into accelerated phase/blast crisis CML. Spred1 KO increased miR-126 in LSKs, expanding leukemic stem cells likely via hyperactivation of the MAPK/ERK pathway, enhancing Bcl-2-dependent oxidative phosphorylation [1]. In melanoma, SPRED1 inactivation in human cell lines and zebrafish melanoma conferred resistance to BRAFV600E inhibition by reactivating MAPK activity [2]. In acute myeloid leukemia (AML), hypermethylation of SPRED1 was detected, and demethylation in THP-1 cells inhibited cell proliferation and promoted differentiation and apoptosis, potentially through the ERK pathway [3]. Also, in AML, SPRED1 expression was downregulated, and its overexpression in THP-1 cells decreased ERK phosphorylation, induced apoptosis, and reduced proliferation [4].
In summary, Spred1 is a key negative regulator of the RAS-MAPK pathway. Model-based research, especially KO mouse models, has revealed its significance in diseases like CML, melanoma, and AML. These studies help understand the biological processes involved in these diseases and may contribute to developing new therapeutic strategies.
References:
1. Qiao, Junjing, Liang, Chen, Zhao, Dandan, Zhang, Bin Amber, Marcucci, Guido. 2021. Spred1 deficit promotes treatment resistance and transformation of chronic phase CML. In Leukemia, 36, 492-506. doi:10.1038/s41375-021-01423-x. https://pubmed.ncbi.nlm.nih.gov/34564700/
2. Ablain, Julien, Liu, Sixue, Moriceau, Gatien, Lo, Roger S, Zon, Leonard I. . SPRED1 deletion confers resistance to MAPK inhibition in melanoma. In The Journal of experimental medicine, 218, . doi:10.1084/jem.20201097. https://pubmed.ncbi.nlm.nih.gov/33306107/
3. Su, Nan, Wang, Yujiao, Lu, Xianglan, Li, Yan, Zhang, Rui. 2022. Methylation of SPRED1: A New Target in Acute Myeloid Leukemia. In Frontiers in oncology, 12, 854192. doi:10.3389/fonc.2022.854192. https://pubmed.ncbi.nlm.nih.gov/35359401/
4. Zhang, Rui, Zhang, Yan, Lu, Xianglan, Yan, Xiaojing, Li, Yan. 2020. SPRED1 Is Downregulated and a Prognostic Biomarker in Adult Acute Myeloid Leukemia. In Frontiers in oncology, 10, 204. doi:10.3389/fonc.2020.00204. https://pubmed.ncbi.nlm.nih.gov/32175275/
5. Brems, Hilde, Pasmant, Eric, Van Minkelen, Rick, Legius, Eric, Messiaen, Ludwine. 2012. Review and update of SPRED1 mutations causing Legius syndrome. In Human mutation, 33, 1538-46. doi:10.1002/humu.22152. https://pubmed.ncbi.nlm.nih.gov/22753041/
6. Chelleri, Cristina, Brolatti, Noemi, De Marco, Patrizia, Zara, Federico, Scala, Marcello. 2024. Novel causative variants in Legius syndrome: SPRED1 Genotype spectrum expansion. In American journal of medical genetics. Part A, 194, e63824. doi:10.1002/ajmg.a.63824. https://pubmed.ncbi.nlm.nih.gov/39031930/
7. Brems, Hilde, Legius, Eric. 2013. Legius syndrome, an Update. Molecular pathology of mutations in SPRED1. In The Keio journal of medicine, 62, 107-12. doi:. https://pubmed.ncbi.nlm.nih.gov/24334617/
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