C57BL/6JCya-Cnksr1em1/Cya
Common Name:
Cnksr1-KO
Product ID:
S-KO-20536
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
Quantity
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Basic Information
Strain Name
Cnksr1-KO
Strain ID
KOCMP-194231-Cnksr1-B6J-VC
Gene Name
Product ID
S-KO-20536
Gene Alias
-
Background
C57BL/6JCya
NCBI ID
Modification
Conventional knockout
Chromosome
4
Phenotype
Document
Application
--
Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Cnksr1em1/Cya mice (Catalog S-KO-20536) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000030645
NCBI RefSeq
NM_001081047
Target Region
Exon 2~3
Size of Effective Region
~1.9 kb
Detailed Document
Overview of Gene Research
Cnksr1, or connector enhancer of kinase suppressor of Ras 1, acts as a scaffold component for receptor tyrosine kinase in mitogen-activated protein kinase (MAPK) cascades [2]. It is involved in several crucial biological processes and disease-related pathways, making it an important gene for functional studies.
In HER2-positive breast cancer cells, degradation of RhoB by the CUL3/KCTD10 ubiquitin ligase complex enables CNKSR1 to interact with PTPRH at the plasma membrane, inactivating EGFR phosphatase activity. Depletion of CUL3 or KCTD10 leads to RhoB-GTP accumulation, its interaction with CNKSR1, and release of activated PTPRH, suggesting a mechanism of PTPRH activation [1]. In pancreatic ductal adenocarcinoma, CNKSR1high cancer cells show resistance to MAPK (MEK) inhibition. MEK inhibition induces CNKSR1 translocation to the plasma membrane, where it interacts with and stabilizes phosphorylated AKT, promoting crosstalk to AKT signaling [3]. In a study on an Iranian family with syndromic autosomal recessive intellectual disability, a novel frameshift mutation in CNKSR1 was detected. Lack of its transcripts and protein was observed in affected patients' lymphoblastoid cells, and RNAi-mediated knockdown of its Drosophila orthologue led to eye and mushroom body structure defects, indicating its role in brain development [2].
In conclusion, Cnksr1 is a key scaffold protein involved in multiple signaling pathways. Its dysregulation is associated with diseases such as breast cancer, pancreatic cancer, and intellectual disability. Studies on gene-modified models like RNAi-mediated knockdown in Drosophila and analysis of mutations in human patients have provided insights into its role in disease-related biological processes, contributing to our understanding of disease mechanisms and potentially guiding future therapeutic strategies.
References:
1. Nishiyama, Kanako, Maekawa, Masashi, Nakagita, Tomoya, Takada, Yasutsugu, Higashiyama, Shigeki. 2021. CNKSR1 serves as a scaffold to activate an EGFR phosphatase via exclusive interaction with RhoB-GTP. In Life science alliance, 4, . doi:10.26508/lsa.202101095. https://pubmed.ncbi.nlm.nih.gov/34187934/
2. Kazeminasab, Somayeh, Taskiran, Ibrahim Ihsan, Fattahi, Zohreh, Najmabadi, Hossein, Kahrizi, Kimia. 2018. CNKSR1 gene defect can cause syndromic autosomal recessive intellectual disability. In American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, 177, 691-699. doi:10.1002/ajmg.b.32648. https://pubmed.ncbi.nlm.nih.gov/30450701/
3. Li, Dandan, Miermont, Anne M, Sable, Rushikesh, Hewitt, Stephen M, Rudloff, Udo. . Scaffolding Protein Connector Enhancer of Kinase Suppressor of Ras 1 (CNKSR1) Regulates MAPK Inhibition Responsiveness in Pancreas Cancer via Crosstalk with AKT Signaling. In Molecular cancer research : MCR, 21, 316-331. doi:10.1158/1541-7786.MCR-21-1036. https://pubmed.ncbi.nlm.nih.gov/36790955/
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