C57BL/6JCya-Notumem1flox/Cya
Common Name:
Notum-flox
Product ID:
S-CKO-16692
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
Quantity
Price:
Contact for Pricing
Basic Information
Strain Name
Notum-flox
Strain ID
CKOCMP-77583-Notum-B6J-VA
Gene Name
Product ID
S-CKO-16692
Gene Alias
5730593N15Rik
Background
C57BL/6JCya
NCBI ID
Modification
Conditional knockout
Chromosome
11
Phenotype
Document
Application
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Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Notumem1flox/Cya mice (Catalog S-CKO-16692) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000106178
NCBI RefSeq
NM_175263
Target Region
Exon 3~9
Size of Effective Region
~3.0 kb
Detailed Document
Overview of Gene Research
Notum, a palmitoleoyl-protein carboxylesterase, is a negative regulator of the Wnt signaling pathway. It acts by removing an essential palmitoleate group from Wnt proteins, thus inhibiting Wnt-FZD receptor-ligand interactions [3,4]. The Wnt signaling pathway is crucial for many cellular processes in development and adult mammalian biology, making Notum's role significant in various biological contexts [5].
In colorectal cancer, Apc-mutant cells highly express Notum. Conditioned medium from these cells suppresses wild-type organoid growth in a NOTUM-dependent manner. Genetic or pharmacological inhibition of NOTUM abrogates the ability of Apc-mutant cells to expand and form intestinal adenomas, indicating its role in the early stages of mutation fixation [1]. In aged intestinal epithelium, Notum produced by Paneth cells decreases stem-ness-maintaining Wnt signaling, impairing regeneration. Genetic targeting or pharmacological inhibition of Notum restores the function of aged intestinal organoids and enhances the regenerative capacity of aged stem cells [2]. In advanced colorectal cancer, NOTUM has different roles depending on the mutation landscape. In APC-null adenomas, it has tumour-suppressive activity, but upon P53 loss and progression to adenocarcinoma, it becomes an oncogene. Pharmacological inhibition of NOTUM effectively arrests primary adenocarcinoma growth and inhibits metastasis [4].
In conclusion, Notum plays a key role in modulating Wnt signaling, which is vital for multiple biological processes. Through gene-knockout or conditional-knockout mouse models and other loss-of-function experiments, Notum has been shown to be involved in disease conditions such as colorectal cancer and age-related intestinal epithelium regeneration decline. Understanding Notum's function provides potential therapeutic strategies for these diseases.
References:
1. Flanagan, Dustin J, Pentinmikko, Nalle, Luopajärvi, Kalle, Katajisto, Pekka, Sansom, Owen J. 2021. NOTUM from Apc-mutant cells biases clonal competition to initiate cancer. In Nature, 594, 430-435. doi:10.1038/s41586-021-03525-z. https://pubmed.ncbi.nlm.nih.gov/34079124/
2. Pentinmikko, Nalle, Iqbal, Sharif, Mana, Miyeko, Yilmaz, Ömer H, Katajisto, Pekka. 2019. Notum produced by Paneth cells attenuates regeneration of aged intestinal epithelium. In Nature, 571, 398-402. doi:10.1038/s41586-019-1383-0. https://pubmed.ncbi.nlm.nih.gov/31292548/
3. Zhao, Yuguang, Jolly, Sarah, Benvegnu, Stefano, Jones, E Yvonne, Fish, Paul V. 2021. Small-molecule inhibitors of carboxylesterase Notum. In Future medicinal chemistry, 13, 1001-1015. doi:10.4155/fmc-2021-0036. https://pubmed.ncbi.nlm.nih.gov/33882714/
4. Tian, Yuhua, Wang, Xin, Cramer, Zvi, Lengner, Christopher J, Li, Ning. 2023. APC and P53 mutations synergise to create a therapeutic vulnerability to NOTUM inhibition in advanced colorectal cancer. In Gut, 72, 2294-2306. doi:10.1136/gutjnl-2022-329140. https://pubmed.ncbi.nlm.nih.gov/37591698/
5. Bayle, Elliott D, Svensson, Fredrik, Atkinson, Benjamin N, Vincent, Jean-Paul, Fish, Paul V. 2021. Carboxylesterase Notum Is a Druggable Target to Modulate Wnt Signaling. In Journal of medicinal chemistry, 64, 4289-4311. doi:10.1021/acs.jmedchem.0c01974. https://pubmed.ncbi.nlm.nih.gov/33783220/
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