C57BL/6JCya-Mcoln1em1flox/Cya
Common Name:
Mcoln1-flox
Product ID:
S-CKO-17235
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
Quantity
Price:
Contact for Pricing
Basic Information
Strain Name
Mcoln1-flox
Strain ID
CKOCMP-94178-Mcoln1-B6J-VA
Gene Name
Product ID
S-CKO-17235
Gene Alias
2210015I05Rik; TRPML1; mucolipidin
Background
C57BL/6JCya
NCBI ID
Modification
Conditional knockout
Chromosome
8
Phenotype
Document
Application
--
Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Mcoln1em1flox/Cya mice (Catalog S-CKO-17235) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000004683
NCBI RefSeq
NM_053177.1
Target Region
Exon 2
Size of Effective Region
~1.5 kb
Detailed Document
Overview of Gene Research
Mcoln1, also known as TRPML1 (mucolipin TRP cation channel 1), is a nonselective cationic channel specifically located in the late endosome and lysosome. It mediates the release of divalent cations like Ca2+, Zn2+ and Fe2+ from the lysosome to the cytosol, playing a pivotal role in regulating numerous cellular events, especially autophagy-a conserved catabolic process for maintaining cytoplasmic integrity. Lysosomes, as terminal compartments, are crucial for autophagy completion, and Mcoln1 controls this process by regulating lysosomal ionic homeostasis [3].
Activating Mcoln1 arrests autophagic flux in cancer cells such as those in pancreatic, breast, gastric cancers, malignant melanoma, and glioma, by disrupting the fusion between autophagosomes and lysosomes, which is achieved by mediating zinc influx. This zinc influx blocks the interaction between STX17 in autophagosomes and VAMP8 in lysosomes. Activating Mcoln1 with agonists also triggers cancer cell death with little effect on normal cells, and in xenograft mice, it suppresses tumor growth [1]. Mcoln1-mediated autophagy inhibition suppresses cancer metastasis in melanoma and glioma cells in vitro and in vivo by evoking the ROS-mediated TP53/p53 pathway [2]. In cardiomyocytes post ischemia-reperfusion (I/R), Mcoln1 activation leads to lysosomal zinc release, blocking autophagic flux, impairing mitochondrial function, and causing cardiomyocyte death. Blocking Mcoln1 channels restores autophagic flux, rescues cardiomyocyte death in vitro, and improves cardiac function in vivo [4].
In summary, Mcoln1 is essential for regulating autophagy through its role in lysosomal ionic regulation. Studies using models (implied by in vitro and in vivo experiments in the references) have revealed its significance in cancer, where it can be targeted to control oncogenic autophagy and metastasis, and in myocardial I/R injury, where targeting it could be a novel therapeutic strategy.
References:
1. Qi, Jiansong, Xing, Yanhong, Liu, Yucheng, Guo, Feng, Wang, Wuyang. 2021. MCOLN1/TRPML1 finely controls oncogenic autophagy in cancer by mediating zinc influx. In Autophagy, 17, 4401-4422. doi:10.1080/15548627.2021.1917132. https://pubmed.ncbi.nlm.nih.gov/33890549/
2. Xing, Yanhong, Wei, Xiangqing, Liu, Yucheng, Qi, Jiansong, Wang, Wuyang. 2021. Autophagy inhibition mediated by MCOLN1/TRPML1 suppresses cancer metastasis via regulating a ROS-driven TP53/p53 pathway. In Autophagy, 18, 1932-1954. doi:10.1080/15548627.2021.2008752. https://pubmed.ncbi.nlm.nih.gov/34878954/
3. Qi, Jiansong, Li, Qingqing, Xin, Tianli, Cui, Derong, Wang, Mengmeng. 2024. MCOLN1/TRPML1 in the lysosome: a promising target for autophagy modulation in diverse diseases. In Autophagy, 20, 1712-1722. doi:10.1080/15548627.2024.2333715. https://pubmed.ncbi.nlm.nih.gov/38522082/
4. Sui, Zhongheng, Wang, Meng-Meng, Xing, Yanhong, Qi, Jiansong, Wang, Wuyang. 2022. Targeting MCOLN1/TRPML1 channels to protect against ischemia-reperfusion injury by restoring the inhibited autophagic flux in cardiomyocytes. In Autophagy, 18, 3053-3055. doi:10.1080/15548627.2022.2072657. https://pubmed.ncbi.nlm.nih.gov/35491864/
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